AUT-00063
| Clinical data | |
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| Other names | AUT-00063 |
| Routes of administration | Oral |
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| Formula | C20H21N3O4 |
| Molar mass | 367.405 g·mol−1 |
AUT00063 (also called AUT-00063) is an investigational small-molecule compound developed by Autifony Therapeutics for hearing loss and tinnitus.[1]
Background and development
AUT00063 was identified as a modulator of Kv3 (Shaw) family potassium channels, which play a role in the firing properties of auditory neurons and are implicated in central auditory hyper-activity hypotheses of tinnitus.[2]
In June 2014 Autifony announced that it had been awarded a £2.2 million grant from the UK's Technology Strategy Board (now Innovate UK) toward a Phase IIa clinical trial in tinnitus patients.[3]
Clinical trials
Tinnitus (QUIET-1)
A randomised, double-blind, placebo-controlled Phase IIa study (EudraCT 2014–002179–27) titled "QUIET-1" enrolled participants with subjective tinnitus to assess efficacy and safety of AUT00063 versus placebo.[4]
However, the trial was terminated early for futility: Autifony announced on 28 April 2016 that headline data from QUIET-1 "confirm lack of efficacy of AUT00063 in the treatment of people with mild-to-moderate tinnitus.".[4]
Mechanism of action
AUT00063 targets Kv3 (Shaw) potassium channels, which are voltage-gated channels expressed in the central auditory pathway and help control rapid repolarization and high-frequency firing of neurons. By modulating these channels, the drug aimed to reduce abnormal spontaneous activity (a proposed substrate of tinnitus) in central auditory circuits.[5]
See also
References
- ^ "Autifony Therapeutics Initiates Phase I Study of Hearing Loss and Tinnitus Medication". Hearing Review. 2013-06-05. Retrieved 2025-11-12.
- ^ Chambers A (2017). "Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage". Scientific Reports. 7 (1) 17496. Bibcode:2017NatSR...717496C. doi:10.1038/s41598-017-17406-x. PMC 5727503. PMID 29235497.
- ^ "Autifony Therapeutics awarded £2.2 million to progress first-in-class drug for tinnitus into Phase IIa study" (PDF). Autifony Therapeutics. Autifony Therapeutics Ltd. 2014-06-04. Retrieved 2025-11-12.
- ^ a b Hall DA, Ray J, Watson J, Sharman A, Hutchison J, Harris P, et al. (June 2019). "A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial". Hearing Research. 377: 153–166. doi:10.1016/j.heares.2019.03.018. PMID 30939361.
- ^ Glait L, Fan W, Stillitano G, Sandridge S, Pilati N, Large C, et al. (April 2018). "Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus". Hearing Research. 361: 36–44. doi:10.1016/j.heares.2018.01.017. PMID 29453003.