AUT-00063(AUT-00063) - 药物靶点：Kv3.1_在研适应症：耳鸣_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AUT00063

靶点

Kv3.1

作用机制

Kv3.1调节剂(电压门控性钾通道蛋白亚型Kv3.1调节剂)

治疗领域

神经系统疾病耳鼻咽喉疾病

在研适应症

耳鸣

非在研适应症

听力损失耳毒性老年性耳聋

原研机构

Autifony Therapeutics Ltd.

在研机构

NIHR Manchester Biomedical Research Centre初创企业

Nottingham University Hospitals Nhs Trust

Sheffield Children's NHS Foundation Trust

非在研机构

Autifony Therapeutics Ltd.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 AUT-00063 相关的临床试验

NCT02832128 / Completed临床2期

A Pilot Double Blind Placebo Controlled Crossover Study to Explore Possible Benefits of AUT00063, An Oral Modulator of Voltage - Gated Potassium Channels , In Adults Post-lingual Unilateral Cochlear Implant Recipients

The objective of this pilot study is to explore whether repeat doses of AUT00063 can provide an indication of improvement in performance of tests across a battery of speech and hearing assessments in cochlear implant users.

开始日期2016-05-01

申办/合作机构

Autifony Therapeutics Ltd.

NCT02345031 / Completed临床2期

A Balanced, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of AUT00063 Versus Placebo in Age-Related Hearing Loss [CLARITY-1 Study]

This study aims to demonstrate that the investigational drug AUT00063 is effective and safe in the treatment of age-related hearing loss.

开始日期2015-01-01

申办/合作机构

Autifony Therapeutics Ltd.

NCT02315508 / Completed临床2期

A Balanced Randomised Placebo Controlled Double-blind Phase IIa Study to Investigate the Efficacy and Safety of AUT00063 Versus Placebo in Subjective Tinnitus

This study aims to demonstrate that the new medicine AUT00063 is effective and safe in the treatment of tinnitus.

开始日期2014-10-01

申办/合作机构

Autifony Therapeutics Ltd.

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100 项与 AUT-00063 相关的临床结果

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100 项与 AUT-00063 相关的转化医学

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100 项与 AUT-00063 相关的专利（医药）

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6

项与 AUT-00063 相关的文献（医药）

2021-03-01·Hearing Research1区 · 医学

Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats

1区 · 医学

Article

作者: Large, Charles H ; Alvaro, Giuseppe S ; Syka, Josef ; Rybalko, Natalia ; Popelář, Jiří ; Šuta, Daniel ; Svobodová Burianová, Jana

AUT00063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K⁺ channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on auditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic startle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug administration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT00063 and AUT00202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT00063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT00063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT00063 and AUT00202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.

2019-06-01·Hearing Research1区 · 医学

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

1区 · 医学

Article

作者: Hall, Deborah A ; Sharman, Alice ; Daniel, Matija ; Millar, Bonnie ; Hutchison, John ; Harris, Peter ; Ray, Jaydip ; Watson, Jeannette ; Large, Charles H

AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.

2018-12-01·Journal of the Association for Research in Otolaryngology1区 · 医学

Evaluation of Possible Effects of a Potassium Channel Modulator on Temporal Processing by Cochlear Implant Listeners

1区 · 医学

Article

作者: Lamping, Wiebke ; Guérit, François ; Deeks, John M ; Harris, Peter ; Saeed, Shakeel R ; Carlyon, Robert P ; Large, Charles H ; Billig, Alexander J

Temporal processing by cochlear implant listeners is degraded and is affected by auditory deprivation. The fast-acting Kv3.1 potassium channel is important for sustained temporally accurate firing and is also susceptible to deprivation, the effects of which can be partially restored in animals by the molecule AUT00063. We report the results of a randomised placebo-controlled double-blind study on psychophysical tests of the effects of AUT00063 on temporal processing by CI listeners. The study measured the upper limit of temporal pitch, gap detection, and discrimination of low rates (centred on 120 pps) for monopolar pulse trains presented to an apical electrode. The upper limit was measured using the optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds were obtained for the other two measures using an adaptive procedure. Twelve CI users (MedEl and Cochlear) were tested before and after two periods of AUT00063 or placebo in a within-subject crossover study. No significant differences occurred between post-drug and post-placebo conditions. This absence of effect occurred despite high test-retest reliability for all three measures, obtained by comparing performance on the two baseline visits, and despite the demonstrated sensitivity of the measures to modest changes in temporal processing obtained in other studies from our laboratory. Hence, we have no evidence that AUT00063 improves temporal processing for the doses and patient population employed.

100 项与 AUT-00063 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
听力损失	临床3期	英国	Autifony Therapeutics Ltd.	2016-05-01
耳毒性	临床3期	英国	Autifony Therapeutics Ltd.	2016-05-01
老年性耳聋	临床3期	美国	Autifony Therapeutics Ltd.	2015-01-01
耳鸣	临床3期	英国	Autifony Therapeutics Ltd.	2014-10-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02345031 (CLARITY-1, CTgov)	临床2期	老年性耳聋	78	AUT00063 (AUT00063 (600 mg Capsules))	繭蓋淵遞衊積夢構鏇淵(遞齋簾憲築網構鹹淵鏇) = 網淵觸築壓遞遞鹹願齋簾齋餘鬱簾夢夢繭鬱窪 (壓鏇衊積鹽簾獵鑰齋顧, 鹹遞廠齋顧餘繭艱積艱 ~ 鬱齋憲範壓憲廠憲蓋鏇) 更多	-	2017-09-19
				Placebo ((AUT00063 Placebo Capsules))	繭蓋淵遞衊積夢構鏇淵(遞齋簾憲築網構鹹淵鏇) = 鏇構範範遞網願憲齋製簾齋餘鬱簾夢夢繭鬱窪 (壓鏇衊積鹽簾獵鑰齋顧, 積壓製齋艱構選餘艱選 ~ 鹽壓夢願製齋壓窪構窪) 更多