OTO-313 in Subjects With Subjective Tinnitus

• ClinicalTrials.gov Identifier: NCT03918109
• Recruitment Status: Completed
• First Posted: April 17, 2019
• Results First Posted: December 23, 2022
• Last Update Posted: December 23, 2022
• Sponsor: Otonomy, Inc.
• Information provided by (Responsible Party): Otonomy, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Tinnitus, Subjective	Drug: OTO-313; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, multicenter
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Phase 1/2 Study of OTO-313 Given as a Single Intratympanic Injection in Subjects With Subjective Tinnitus
• Actual Study Start Date: April 4, 2019
• Actual Primary Completion Date: May 29, 2020
• Actual Study Completion Date: May 29, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Audiometry - Pure Tone Average Done Over 1000, 2000 and 4000 Hertz (HZ) [ Time Frame: 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.
2. 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)). [ Time Frame: 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.

Other Outcome Measures:

1. Change From Baseline in Tinnitus Functional Index (TFI) [ Time Frame: 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.
2. Patient Global Impression of Change (PGIC) [ Time Frame: 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

House Clinic

Los Angeles, California, United States, 90057

California Head & Neck Specialists

San Diego, California, United States, 92121

United States, Colorado

Colorado ENT and Allergy

Colorado Springs, Colorado, United States, 80909

United States, Florida

Silverstein Institute/Ear Research Foundation

Sarasota, Florida, United States, 34239

United States, Illinois

ChicagoENT

Chicago, Illinois, United States, 60657

United States, Kentucky

Advanced ENT and Allergy

Louisville, Kentucky, United States, 40207

United States, Louisiana

Tandem Clinical Research, LLC

Marrero, Louisiana, United States, 70072

United States, New Jersey

Summit Medical Group

Berkeley Heights, New Jersey, United States, 10882

United States, New York

Dent Neurosciences Research Center

Amherst, New York, United States, 14226

Northwell Health, Hearing & Speech Center

New Hyde Park, New York, United States, 11042

Northwell Health at ENT and Allergy Associates

White Plains, New York, United States, 10605

United States, North Carolina

Charlotte Eye Ear Nose & Throat Associates

Charlotte, North Carolina, United States, 28210

Piedmont Ear, Nose, and Throat Associates

Winston-Salem, North Carolina, United States, 27103

United States, Texas

Worldwide Clinical Trials

San Antonio, Texas, United States, 78217

United States, Utah

Chrysalis Clinical Research

Saint George, Utah, United States, 84790

United States, West Virginia

WVU Medicine

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

Otonomy, Inc.

  Study Documents (Full-Text)

Documents provided by Otonomy, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] May 15, 2019

More Information

• Responsible Party: Otonomy, Inc.
• ClinicalTrials.gov Identifier: NCT03918109
• Other Study ID Numbers: 313-201901
• First Posted: April 17, 2019
• Results First Posted: December 23, 2022
• Last Update Posted: December 23, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otonomy, Inc.:

tinnitus, intratympanic injection, gacyclidine

Additional relevant MeSH terms:

Tinnitus; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases