Intratympanic Administration of OTO-313 Reduces Tinnitus in Patients With Moderate to Severe, Persistent Tinnitus: A Phase 1/2 Study

Maxwell, Kenneth; Robinson, James M.; Hoffmann, Ines; Hou, Huiying J.; Searchfield, Grant; Baguley, David M.; McMurry, Gordon; Piu, Fabrice; Anderson, Jeffery J.

Abstract

Objective:
To evaluate the safety and exploratory efficacy of intratympanic administration of OTO-313 in patients with tinnitus.

Study Design:
Single intratympanic injection of OTO-313 evaluated in a randomized, double-blind, placebo-controlled Phase 1/2 clinical study.

Setting:
Tertiary referral centers.

Patients:
Patients with unilateral tinnitus (moderate–severe) with tinnitus duration 1 to 6 months.

Interventions:
Intratympanic OTO-313.

Main Outcome Measures:
Safety and change from baseline in tinnitus functional index (TFI), daily ratings of tinnitus loudness and annoyance, and patient global impression of change (PGIC).

Results:
OTO-313 was well-tolerated with lower incidence of adverse events than placebo. Mean TFI reduction from baseline favored OTO-313 at Week 2, 4, and 8. A clinically meaningful, 13-point improvement on the TFI was observed in 43% (6/14) of OTO-313 patients at both Weeks 4 and 8 versus 13% (2/16) of placebo patients (ad hoc responder analysis, p-value < 0.05). Reductions in daily ratings of tinnitus loudness and annoyance favored OTO-313 compared with placebo. In OTO-313 responders, a strong correlation existed between change from baseline in TFI score and changes in tinnitus loudness, tinnitus annoyance, and PGIC.

Conclusions:
OTO-313 was well-tolerated and demonstrated a higher proportion of responders than placebo across consecutive visits (Weeks 4 and 8) supporting further clinical development of OTO-313 for the treatment of tinnitus.

Citation

Maxwell, K., Robinson, J. M., Hoffmann, I., Hou, H. J., Searchfield, G., Baguley, D. M., …Anderson, J. J. (2021). Intratympanic Administration of OTO-313 Reduces Tinnitus in Patients With Moderate to Severe, Persistent Tinnitus: A Phase 1/2 Study. Otology and Neurotology, 42(10), e1625-e1633. https://doi.org/10.1097/mao.0000000000003369

• Journal Article Type: Article
• Acceptance Date: Aug 9, 2021
• Online Publication Date: Oct 8, 2021
• Publication Date: Dec 1, 2021
• Deposit Date: Aug 17, 2021
• Publicly Available Date: Oct 9, 2022
• Journal: Otology and Neurotology
• Print ISSN: 1531-7129
• Electronic ISSN: 1537-4505
• Publisher: Ovid Technologies (Wolters Kluwer Health)
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 10
• Pages: e1625-e1633
• DOI: https://doi.org/10.1097/mao.0000000000003369
• Keywords: Neurology (clinical); Sensory Systems; Otorhinolaryngology
• Public URL: https://nottingham-repository.worktribe.com/output/6054966
• Publisher URL: https://journals.lww.com/otology-neurotology/Abstract/9000/Intratympanic_Administration_of_OTO_313_Reduces.95498.aspx