# 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

> **NIH NIH U01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $657,906

## Abstract

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).

## Key facts

- **NIH application ID:** 10426862
- **Project number:** 1U01DC020175-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Edwin W Rubel
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $657,906
- **Award type:** 1
- **Project period:** 2022-09-19 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426862

## Citation

> US National Institutes of Health, RePORTER application 10426862, 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 (1U01DC020175-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426862. Licensed CC0.

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