Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention of Drug-Induced Hearing Loss in Patients Receiving Intravenous Amikacin for Treatment of Non-Tuberculous Mycobacterium Disease

The goal of this clinical trial is to test the effectiveness of the study drug, ORC-13361, in preventing hearing loss in patients with NTM infection who are undergoing treatment with IV amikacin therapy. The main question this study aims to answer is:
Is ORC-13661 effective for preventing or lessening hearing loss induced by amikacin treatment?
Is ORC-13661 effective for preventing or lessening other measures of hearing impairment?
Participants will be asked to take a study drug while they are being treated with IV amikacin. Participants will take study drug for 90 days or until the end of their amikacin treatment, whichever comes first. During this time, researchers will gather clinical data on the participants' health.
Researchers will compare three groups - two groups taking different doses of the study drug and one group taking a placebo drug - to see if dose of drug has any effect on preventing hearing loss. A placebo is a look-alike substance that contains no active drug.

开始日期2024-06-01

申办/合作机构

Oregon Health & Science University

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100 项与 BPN-13661 相关的临床结果

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100 项与 BPN-13661 相关的转化医学

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100 项与 BPN-13661 相关的专利（医药）

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项与 BPN-13661 相关的文献（医药）

2020-01-01·International Journal of Immunopathology and Pharmacology

Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: A scoping review

Review

作者: Szczepek, Agnieszka J ; Hatzopoulos, Stavros ; Skarzynska, Magda ; Domarecka, Ewa

Aim: The present review aimed to consolidate and analyze the recent information about the use of zebrafish in studies concerning cisplatin-induced ototoxicity and otoprotection. Material and methods: The PubMed, Web of Science, and Scopus databanks were searched using the following MESH terms: zebrafish, cisplatin, ototoxicity. The identified publications were screened according to inclusion and exclusion criteria and the 26 qualifying manuscripts were included in the full-text analysis. The experimental protocols, including cisplatin concentrations, the exposure duration and the outcome measurements used in zebrafish larvae studies, were evaluated and the reported knowledge was summarized. Results: Twenty-six substances protecting from cisplatin-induced toxicity were identified with the use of zebrafish larvae. These substances include quinine, salvianolic acid B, berbamine 6, benzamil, quercetin, dexmedetomidine, dexamethsanone, quinoxaline, edaravone, apocynin, dimethyl sulfoxide, KR-22335, SRT1720, ORC-13661, 3-MA, D-methionine, mdivi-1, FUT-175, rapamycin, Z-LLF-CHO, ATX, NAC, CYM-5478, CHCP1, CHCP2 and leupeptin. The otoprotective effects of compounds were attributed to their anti-ROS, anti-apoptotic and cisplatin uptake-blocking properties. The broadest range of protection was achieved when the experimental flow used preconditioning with an otoprotective compound and later a co-incubation with cisplatin. Protection against a high concentration of cisplatin was observed only in protocols using short exposure times (4 and 6 h). Conclusions: The data extracted from the selected papers confirm that despite the differences between the human and the zebra fish hearing thresholds (as affected by cisplatin), the sensory cells of zebrafish and larval zebrafish are a valuable tool which could be used: (i) for the discovery of novel otoprotective substances and compounds; (ii) to screen their side effects and (iii) to extend the knowledge on the mechanisms of cisplatin-induced inner ear damage. For future studies, the development of a consensus experimental protocol is highly recommended.

2019-08-08·JCI Insight1区 · 医学

ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

1区 · 医学

ArticleOA

作者: Wu, Patricia ; Simon, Julian A ; Kitcher, Siân R ; Kirkwood, Nerissa K ; Camci, Esra D ; Rubel, Edwin W ; Gibson, Robin M ; Richardson, Guy P ; Redila, Van A ; Raible, David W ; Kros, Corné J

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins.

Frontiers in Molecular Neuroscience

An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics

Article

作者: Simon, Julian A ; Tong, Ling ; Bellairs, Joseph A ; Webster, Alyssa ; Wu, Patricia ; Rubel, Edwin W ; Raible, David W ; Redila, Van A

There are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize in vivo aminoglycoside toxicity. We demonstrate that postnatal day 5 mice, like older mice with functional hearing, show uptake and retention of G418-TR in cochlear hair cells following systemic injection. When we compare G418-TR uptake in other tissues, we find that kidney proximal tubule cells show similar retention. Using ORC-13661, an investigational hearing protection drug, we demonstrate in vivo inhibition of aminoglycoside uptake in mammalian hair cells. This work establishes how systemically administered fluorescently labeled ototoxins in the neonatal mouse can reveal important details about ototoxic drugs and protective therapeutics.

100 项与 BPN-13661 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
非结核分枝杆菌感染	临床2期	美国	Oricula Therapeutics LLC	2024-06-01
耳毒性	临床2期	美国	Oricula Therapeutics LLC	2024-06-01
耳聋	临床1期	美国	Oricula Therapeutics LLC	2022-01-30
听力损失	临床申请	-	University of Washington Bothell	-
神经性听力损失	药物发现	美国	Oricula Therapeutics LLC	-