Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention of Ototoxicity in Patients Receiving Intravenous Amikacin for Treatment of Non-Tuberculous Mycobacterium Infection

ORC-13661预防静脉阿米卡星治疗非结核分枝杆菌感染患者耳毒性的有效性和安全性的2期研究

• 批准号: 10426862
• 负责人: Edwin W Rubel
• 金额: $ 65.79万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426862
• 关键词: Adult; Adverse event; Aftercare; Air; Amikacin; Aminoglycoside Antibiotics; Aminoglycosides; Animal Model; Antibiotic Therapy; Antibiotics; Auditory Threshold; Azithromycin; Bronchiectasis; Canis familiaris; Chemicals; Chronic; Chronic Disease; Clarithromycin; Clinical; Cochlea; Communicable Diseases; Control Animal; Data Reporting; Deterioration; Diagnosis; Disease; Disease Progression; Dose; Double-Blind Method; Drug Design; Drug Exposure; Drug Kinetics; Elderly; Electrocardiogram; Equilibrium; Equipment and supply inventories; Evaluation; Exposure to; FDA approved; Frequencies; Genus Mycobacterium; Goals; Gram-Negative Bacteria; Guidelines; Hair Cells; Half-Life; Health; Hearing; Hearing Protection; Human Volunteers; In Vitro; Intravenous; Laboratories; Laboratory Finding; Legal patent; Life; Lung; Measurable; Measures; Metabolic; Mind; Multi-Institutional Clinical Trial; Mus; Mycobacterium Infections; Neonatal; Oral; Oral Administration; Organ of Corti; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Placebo Control; Plasma; Prevention; Publishing; Quality of life; Randomized; Rattus; Research; Rifampin; Safety; Sensorineural Hearing Loss; Sensory Hair; Serious Adverse Event; Swimming; Symptoms; Testing; Therapeutic Index; Time; Tinnitus; Toxic effect; Toxicology; Treatment Protocols; United States; Universities; Vertigo; Washington; Woman; Work; Zebrafish; aminoglycoside-induced ototoxicity; awake; bactericide; bone; chronic infection; clinically relevant; effective therapy; effectiveness evaluation; efficacy evaluation; efficacy study; experimental study; healthy volunteer; hearing impairment; in vivo; indexing; men; neonatal mice; non-tuberculosis mycobacteria; novel; novel therapeutics; ototoxicity; overtreatment; phase 1 testing; phase 2 study; pre-clinical; prevent; prevent hearing loss; primary endpoint; programs; response; safety study; secondary endpoint; side effect; small molecule; speech in noise; tool; treatment duration

PROJECT SUMMARY ORC-13661 is a new chemical entity being developed to prevent hearing loss in patients exposed to aminoglycoside antibiotics (AGs). AGs are an important class of broad spectrum antibiotics especially effective against gram-negative bacteria and Mycobacteria. Unfortunately, as many as 20% of patients administered parenteral AGs for over 5 days suffer permanent, measurable hearing loss, as do upwards of 60% of patients on long term therapy. Largely because of the ototoxic side effects, AGs are currently administered only for life threatening situations or where they are the only effective treatment. At this time there are no FDA approved drugs that have been shown to prevent any form of sensorineural hearing loss. Preventing AG-induced hearing loss would be of enormous benefit patients currently being treated with AGs. It would also allow this inexpensive and effective but underused class of antibiotics to be used more routinely. Oral ORC-13661was developed from a small molecule screen aimed finding a way to mitigate AG-induced hair cell toxicity. It is robustly effective at preventing hearing loss in rats treated with prolonged high dose AGs. ORC-13661 has completed nonclinical evaluation and Phase 1 testing in normal healthy volunteers. Pulmonary and disseminated non-tuberculous Mycobacteria (NTM) infections are chronic infectious diseases that develop progressively over time, and require prolonged parenteral AG therapy to achieve control or a cure. Current guidelines recommend parenteral aminoglycoside (AG) therapy, usually a 90 day course of amikacin, for patients with severe manifestations of the disease, particularly bronchiectasis. We propose a randomized, double-blind, placebo-controlled, multicenter, phase 2 study of ORC-13661 administered orally in conjunction with intravenously administered amikacin to patients with severe NTM infections. The goal of this to evaluate the efficacy of ORC-13661 for mitigation or prevention of ototoxicity. Primary and secondary endpoints are changes in between baseline measures if hearing thresholds and hearing in noise taken prior to drug treatment and after treatment is discontinued in groups of patients treated with amikacin alone or with amikacin plus ORC-13661. Additional evaluations will changes in patient perceived hearing and balance health and the safety and tolerability of ORC-13661 in patients with NTM as assessed by AEs, clinical laboratory findings, vital signs, and electrocardiogram (ECG).

项目总结