U01DC020175

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 - 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 to 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-13661 was developed from a small molecule screen aimed at 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 study is to evaluate the efficacy of ORC-13661 for mitigation or prevention of ototoxicity.

Primary and secondary endpoints are changes in baseline measures of 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 include changes in patient-perceived hearing and balance health and the safety and tolerability of ORC-13661 in patients with NTM as assessed by adverse events, clinical laboratory findings, vital signs, and electrocardiogram (ECG).

Oregon Health & Science University

TO INVESTIGATE SOLUTIONS TO PROBLEMS DIRECTLY RELEVANT TO INDIVIDUALS WITH DEAFNESS OR DISORDERS OF HUMAN COMMUNICATION IN THE AREAS OF HEARING, BALANCE, SMELL, TASTE, VOICE, SPEECH, AND LANGUAGE. THE NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS (NIDCD) SUPPORTS RESEARCH AND RESEARCH TRAINING, INCLUDING INVESTIGATION INTO THE ETIOLOGY, PATHOLOGY, DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES, PRIMARILY THROUGH THE SUPPORT OF BASIC AND APPLIED RESEARCH IN ANATOMY, AUDIOLOGY, BIOCHEMISTRY, BIOENGINEERING, EPIDEMIOLOGY, GENETICS, IMMUNOLOGY, MICROBIOLOGY, MOLECULAR BIOLOGY, THE NEUROSCIENCES, OTOLARYNGOLOGY, PSYCHOLOGY, PHARMACOLOGY, PHYSIOLOGY, PSYCHOPHYSICS, SPEECH-LANGUAGE PATHOLOGY, AND OTHER SCIENTIFIC DISCIPLINES. THE NIDCD SUPPORTS: (1) RESEARCH INTO THE EVALUATION OF TECHNIQUES AND DEVICES USED IN DIAGNOSIS, TREATMENT, REHABILITATION, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES, (2) RESEARCH INTO PREVENTION AND EARLY DETECTION AND DIAGNOSIS OF HEARING LOSS AND SPEECH, VOICE, AND LANGUAGE DISORDERS AND RESEARCH INTO PREVENTING THE EFFECTS OF SUCH DISORDERS BY MEANS OF APPROPRIATE REFERRAL AND REHABILITATION, (3) RESEARCH INTO THE DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES IN THE ELDERLY POPULATION AND ITS REHABILITATION TO ENSURE CONTINUED EFFECTIVE COMMUNICATION SKILLS, AND (4) RESEARCH TO EXPAND KNOWLEDGE OF THE EFFECTS OF ENVIRONMENTAL AGENTS THAT INFLUENCE HEARING OR OTHER COMMUNICATION PROCESSES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO ENCOURAGE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.173 - Research Related to Deafness and Communication Disorders

National Institute on Deafness and Other Communication Disorders (NIDCD) [HHS - NIH]

Portland, Oregon 972393011 United States

Single Zip Code

NIDCD Cooperative Agreement for Clinical Trials in Communication Disorders (U01 - Clinical Trial Required) (PAR-21-064)

Amendment Since initial award the total obligations have increased 487% from $657,906 to $3,863,432.