OTO-313 in Subjects With Subjective Tinnitus

A Randomized, Double-blind, Placebo-controlled Phase 1/2 Study of OTO-313 Given as a Single Intratympanic Injection in Subjects With Subjective Tinnitus

The purpose of this study is to evaluate the safety, tolerability, plasma pharmacokinetics (PK), and exploratory efficacy of OTO-313 administered as an intratympanic injection for the treatment of subjective tinnitus.

Study Overview

• Status: Completed
• Conditions: Tinnitus, Subjective
• Intervention / Treatment: Drug: OTO-313; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • House Clinic
    • San Diego, California, United States, 92121
      • California Head & Neck Specialists
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Colorado ENT and Allergy
  • Florida
    • Sarasota, Florida, United States, 34239
      • Silverstein Institute/Ear Research Foundation
  • Illinois
    • Chicago, Illinois, United States, 60657
      • ChicagoENT
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Advanced ENT and Allergy
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 10882
      • Summit Medical Group
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • New Hyde Park, New York, United States, 11042
      • Northwell Health, Hearing & Speech Center
    • White Plains, New York, United States, 10605
      • Northwell Health at ENT and Allergy Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose & Throat Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Ear, Nose, and Throat Associates
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials
  • Utah
    • Saint George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • WVU Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has subjective unilateral tinnitus and is consistently aware of their tinnitus throughout much of the waking day.
• Subject is able to use the electronic diary to complete their daily tinnitus ratings
• Subject's tinnitus is likely of cochlear origin, e.g., associated with sensorineural hearing loss; acute hearing loss from noise trauma, barotrauma, or traumatic cochlear injury (acute acoustic trauma, blast trauma, middle ear surgery, inner ear barotrauma); age-related hearing loss; resolved otitis media; ototoxic drug exposure.
• Subject is willing to comply with the protocol and attend all study visits.

Exclusion Criteria:

• Subject has pulsatile tinnitus, tinnitus resulting from traumatic head or neck injury, or tinnitus resulting from a tumor or stroke.
• Subject is pregnant or lactating.
• Subject has other clinically significant illness, medical condition or medical history at Screening or Baseline (Day 1) that, in the Investigator's opinion, would likely reduce the safety of study participation or compliance with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; single intratympanic injection of placebo
Experimental: OTO-313	Drug: OTO-313; single intratympanic injection of gacyclidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiometry - Pure Tone Average Done Over 1000, 2000 and 4000 Hertz (HZ)	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.	Up to end of study (Part A - Day 29 [4 weeks after dosing]), (Part B - Day 57 [8 weeks after dosing])
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)).	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.	Up to end of study (Part A - Day 29 [4 weeks after the injection], Part B - Day 57 [8 weeks after the injection])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Pharmacokinetics (PK)	Concentrations of gacyclidine in plasma	Specified timepoints for the first 24 hours and 1 week later

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tinnitus Functional Index (TFI)	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.	Up to the End of Study Visit (Part A - Day 29 [4 weeks after the injection]), (Part B - Day 57 [8 weeks after injection])
Patient Global Impression of Change (PGIC)	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	Measured at the end of study visit (Part A - Day 29 [4 weeks after injection]), (Part B - Day 57 [8 weeks after injection]).

Collaborators and Investigators

• Sponsor: Otonomy, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2019
• Primary Completion (Actual): May 29, 2020
• Study Completion (Actual): May 29, 2020

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: tinnitus, intratympanic injection, gacyclidine
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: 313-201901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No