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Ototoxicity, Drug-InducedPhase 2NCT05730283

Prevention of Ototoxicity in NTM Patients Treated With IV Amikacin

A Phase 2 study testing ORC-13661 in people with Ototoxicity, Drug-Induced, run by Kevin Winthrop at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Ototoxicity, Drug-Induced
What is being tested?
ORC-13661
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
105 participants
Where
8 sitesUnited States
Study dates
2 Jun 2025to 29 Feb 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Providing informed consent, documented by signing and dating the currently valid informed consent form.
  • Considered by the Investigator to have unimpaired consent capacity, without reliance on a legally authorized representative.
  • Stated willingness and ability to comply with study procedures and availability for the duration of the study.
  • Aged > 18 and < 80.
  • NTM infection meeting current Pulmonary NTM guidelines from the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) for systemic (IV) aminoglycoside therapy.
  • Anticipated duration of IV amikacin treatment of at least 30 days at time of study entry.
Show all 9Show fewer
  • Statement of ability to take oral medication and adhere to the daily dosing regimen.
  • For females of reproductive potential: If they are of childbearing potential, they must agree in writing to practice an effective double barrier method of contraception from the signing of the informed consent form until 1 month following discontinuation of study drug treatment or agree to practice true abstinence, when this is consistent with the preferred and usual lifestyle of the subject.
  • For males of reproductive potential: Agree to practice effective barrier contraception from the signing of the informed consent form until 3 months (one spermatogenesis cycle) following the last dose of study drug or agree to practice true abstinence.

Who cannot join

  • Received a systemic aminoglycoside antibiotic within 6 months prior to planned first dose of amikacin.
  • ECG at Screening or prior to randomization (mean of triplicate values) with QT interval corrected using Fridericia's formula (QTcF interval) ≥ 450 msec.
  • ECG at Screening or prior to randomization with abnormalities that, in the Investigator's judgment, might predispose patient to clinically significant arrhythmia.
  • Patients taking strong CYP3A4 inducers such as rifampin and rifabutin in the 7 days prior to randomization or have the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inducers during the study. If an additional antibiotic is needed, then azithromycin will be used.
  • Patients taking strong CYP3A4 inhibitors such as clarithromycin in the 7 days prior to randomization or the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inhibitors during the study. If an additional antibiotic is needed, then azithromycin will be used.
  • Patients taking clofazimine or bedaquiline AND who also have congestive heart failure, significant ventricular arrhythmia, uncorrected hypokalemia, or ECG (single at Screening, mean of triplicate prior to randomization) showing QRS > 120 msec or heart rate < 50 bpm.
Show all 22Show fewer
  • Patients with amikacin exposure within the 6 months prior to randomization.
  • Patients with known amikacin resistance (MIC >64)
  • Progressive liver disease (Child-Pugh B or C) which would affect or invalidate interpretation of change from the baseline liver function tests over the course of the study.
  • Signs of disturbed integrity of the tympanic membrane, determined by otoscopy or tympanometry, including chronic perforation or middle ear or ear canal inflammation or effusion.
  • History of congenital hearing loss, otological surgery (excluding myringotomy tubes or simple tympanoplasty healed and currently intact), sudden hearing loss, or Meniere's disease.
  • Bilateral profound hearing loss (>90 Decibels [dB] HL) at all test frequencies.
  • Conductive hearing loss evidenced by average air-bone-gaps >15 dB HL for 0.25-4.0 kilohertz (kHz)
  • History of active malignancy, either untreated or under active treatment.
  • History of risk factors for Torsades des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  • Venous access not adequate for performance of study procedures.
  • Presence of any circumstance, condition, ECG or laboratory finding that, based on investigator judgment, would interfere with study procedures or assessments or present to the patient an unreasonable risk from participation in this study.
  • Current or anticipated use of excluded concomitant medications as specified in Section 6.5.
  • Pregnant or lactating.
  • Female of childbearing potential who does not have a negative serum pregnancy test and does not agree in writing to using a double barrier method of contraception.
  • Female relying on menopausal status for contraception who does not have Follicle-Stimulating Hormone (FSH) level consistent with that condition and who does not agree in writing to using a double barrier method of contraception.
  • Currently under correctional supervision (imprisoned, on probation or parole).

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Daniel Bouchat contact

503-494-2568

johdanie@ohsu.edu

Violet Tiffee contact

503-494-1433

tiffee@ohsu.edu

8 sites in 1 country

United States8 sites, 7 recruiting

  • Johns Hopkins University

    Baltimore, Maryland, 21224

    Pooja Akoijam, 410-955-1201, pakoija1@jh.edu

    Deya Chatterji, 410-955-1201, dchatte5@jh.edu

    Recruiting

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

    Cameron Mathison, 843-792-7156, mathisoc@musc.edu

    Anna Lares, laresa@musc.edu

    Recruiting

  • National Jewish Health

    Denver, Colorado, 80206

    Shane Hopkins, RN, 303-270-2622, hopkinss@NJHealth.org

    Cindy Wainscoat, RN, WainscoatC@NJHealth.org

    Recruiting

  • Northwell Health

    Manhasset, New York, 11030

    Andrew Diaz, 516-562-3361, ADiaz34@northwell.edu

    Jessica Rao, 516-562-3363, JRao@Northwell.edu

    Recruiting

  • Oregon Health & Science University

    Portland, Oregon, 97239

    Violet Tiffee, 503-494-1433, tiffee@ohsu.edu

    Daniel Bouchat, 503-494-2568, johdanie@ohsu.edu

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Withdrawn

  • University of California, San Francisco

    San Francisco, California, 94143

    Amira Flores Banuelos, 415-502-0276, amira.floresbanuelos@ucsf.edu

    Catherine DeVoe, MD

    Recruiting

  • University of Texas Health Science Center

    Tyler, Texas, 75708

    Kimberly Greenlee, 903-877-5986, Kimberly.Greenlee@uthct.edu

    Devanshi Mehta, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase 2 Study of the Efficacy and Safety of ORC-13661 for the Prevention of Drug-Induced Hearing Loss in Patients Receiving Intravenous Amikacin Therapy for 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?
Read more

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.

Read the detailed description

Nontuberculous mycobacteria (NTM) are environmental bacteria that can cause chronic, debilitating pulmonary disease, primarily affecting those over age 60. In more severe cases of NTM infection, patients are given a therapy with parenteral aminoglycoside antibiotics (AGs), to achieve control or cure. Amikacin is the most commonly used aminoglycoside for treatment in this setting, however it is limited by in its use by its tendency to cause ototoxicity including hearing loss and/or vestibular dysfunction. Ototoxicity refers to substances (i.e. medications) which are damaging to the inner ear sensory cells and may result in functional hearing loss and other negative effects.

This main goal of this study is to test the effectiveness of the study drug, ORC-13661, a small molecule compound being developed as an adjunct therapy to be administered during AG use in order to prevent associated ototoxicity. This study is a randomized, double-blind, placebo-controlled, multicenter, dose-ranging clinical trial to compare the effects and safety of ORC-13661 in preventing or mitigating hearing in patients taking amikacin.

105 participants will be enrolled across 5 enrolling sites over the course of the study. Participants will be randomized in equal numbers between three different study arms: high-dose ORC-13661, low-dose ORC-13661, and placebo. Participants will take study drug for 90 days from the start of their amikacin treatment or until their amikacin treatment ends, whichever comes first.

The primary outcome of this study is prevention or mitigation of amikacin-induced ototoxicity. Secondary outcomes include changes in speech perception, auditory and balance effects, and quality of hearing.

Being tested
ORC-13661, Placebo
Keywords
NTM, nontuberculous mycobacteria, ototoxicity, hearing loss
Medical subject headings
Ototoxicity, Hearing Loss

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ORC-13661Drug

    High-dose intervention (30mg daily)

  • ORC-13661Drug

    Low-dose intervention (12mg daily)

  • PlaceboDrug

    Placebo intervention

Study groups in NCT05730283
Study groupRoleWhat they receive
High Dose ORC-13661ExperimentalThis arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 150mg followed by a daily dose of 30mg. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Receives: Drug: ORC-13661
Low Dose ORC-13661ExperimentalThis arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 60mg capsules followed by a daily dose of 12mg capsules. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Receives: Drug: ORC-13661
PlaceboPlacebo comparatorThis arm is a daily treatment regimen of a placebo with a loading dose and a daily dose of placebo capsules to match the treatment arms. Placebo regimen will run concurrently with treatment with IV amikacin. Placebo regimen will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mitigation or Prevention of Ototoxicity

    Outcome is measured by changes from baseline using the American Speech-Language-Hearing Association (ASHA) shift criterion in patients with NTM disease undergoing treatment with IV amikacin therapy

    Measured: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Secondary outcomes (3)

  1. Mitigation or Prevention of hearing impairment with regards to speech perceptions

    Outcome is measured by changes to patient's speech perceptions using the High Frequency Digits-in-Noise (HF-DIN) test

    Measured: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

  2. Mitigation or Prevention of hearing impairment with regards to perceived auditory and balance effects

    Outcome is measured by changes to patient's tinnitus using the Modified-Tinnitus Ototoxicity Monitoring Interview (TOMI)

    Measured: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

  3. Mitigation or Prevention of hearing impairment with regards to speech, spatial and quality of hearing

    Outcome is measured by changes to patient's Speech, Spatial and Quality of Hearing Scale (SSQ12)

    Measured: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2023
  2. Study start2 Jun 2025
  3. Primary completion29 Feb 2028 (estimated)
  4. Study completion29 Feb 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
105 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05730283
Sponsor's protocol ID
SOUNDS Trial
Other IDs
U01DC020175
Status last verified
Sep 2026
First submitted
7 Feb 2023
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chowdhury S, Owens KN, Herr RJ, Jiang Q, Chen X, Johnson G, Groppi VE, Raible DW, Rubel EW, Simon JA. Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss. J Med Chem. 2018 Jan 11;61(1):84-97. doi: 10.1021/acs.jmedchem.7b00932. Epub 2017 Oct 27.

    PubMed 28992413

  • Garinis A, Gleser M, Johns A, Larsen E, Vachhani J. Prospective cohort study of ototoxicity in persons with cystic fibrosis following a single course of intravenous tobramycin. J Cyst Fibros. 2021 Mar;20(2):278-283. doi: 10.1016/j.jcf.2020.07.001. Epub 2020 Jul 24.

    PubMed 32713806

  • Gleser MA, Zettner EM. Negative hearing effects of a single course of IV aminoglycoside therapy in cystic fibrosis patients. Int J Audiol. 2018 Dec;57(12):917-924. doi: 10.1080/14992027.2018.1514537. Epub 2018 Nov 1.

    PubMed 30382794

  • Jarand J, Levin A, Zhang L, Huitt G, Mitchell JD, Daley CL. Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease. Clin Infect Dis. 2011 Mar 1;52(5):565-71. doi: 10.1093/cid/ciq237.

    PubMed 21292659

  • Kitcher SR, Kirkwood NK, Camci ED, Wu P, Gibson RM, Redila VA, Simon JA, Rubel EW, Raible DW, Richardson GP, Kros CJ. ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity. JCI Insight. 2019 Aug 8;4(15):e126764. doi: 10.1172/jci.insight.126764. eCollection 2019 Aug 8.

    PubMed 31391343

  • Potgieter JM, Swanepoel W, Smits C. Evaluating a smartphone digits-in-noise test as part of the audiometric test battery. S Afr J Commun Disord. 2018 May 21;65(1):e1-e6. doi: 10.4102/sajcd.v65i1.574.

    PubMed 29781704

  • Smits C, Theo Goverts S, Festen JM. The digits-in-noise test: assessing auditory speech recognition abilities in noise. J Acoust Soc Am. 2013 Mar;133(3):1693-706. doi: 10.1121/1.4789933.

    PubMed 23464039

  • Zettner EM, Gleser MA. Progressive Hearing Loss among Patients with Cystic Fibrosis and Parenteral Aminoglycoside Treatment. Otolaryngol Head Neck Surg. 2018 Nov;159(5):887-894. doi: 10.1177/0194599818782444. Epub 2018 Jun 19.

    PubMed 29914288

  • Carhart R, Jerger, J. Preferred method for clinical determination of pure-tone thresholds. J Speech Hear Disord. 1959; 24: 330-345.

  • Kemp DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am. 1978 Nov;64(5):1386-91. doi: 10.1121/1.382104.

    PubMed 744838

  • Chisholm J, Lacey C, Zalewski C, Christensen J, Wafa T, Kim J, Beri A, Fennelly K, Olivier K, Brewer C. Factors Influencing the Prevalence of Amikacin Ototoxicity. Poster presented at the National Center for Rehabilitative Research (NCRAR) Biennial Conference, Ototoxicity and Noise Damage: Translating Preclinical Findings to Audiological Management. 2019 September 25-27; Portland, Oregon.

  • Lacey C, Chisholm J, Zalewski C, Christensen J, Wafa T, Kim HJ, Beri A, Olivier K, Fennelly K, Brewer C. Amikacin Ototoxicity: Risk Factors and Sensitivity of Grading Scales. Poster presented at The NIH Summer Poster Day. 2019 August 8; Bethesda, Maryland.

  • Prasad K, Borre ED, Dillard LK, Ayer A, Der C, Bainbridge KE, McMahon CM, Tucci DL, Wilson BS, Schmidler GDS, Saunders J. Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid review. Lancet Glob Health. 2024 Feb;12(2):e217-e225. doi: 10.1016/S2214-109X(23)00514-4.

    PubMed 38245112

  • Bellairs JA, Redila VA, Wu P, Tong L, Webster A, Simon JA, Rubel EW, Raible DW. An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics. Front Mol Neurosci. 2022 Jul 18;15:944846. doi: 10.3389/fnmol.2022.944846. eCollection 2022.

    PubMed 35923755

  • Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, Knisely AJ, Simon JA, Rubel EW, Raible DW. Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death. PLoS Genet. 2008 Feb 29;4(2):e1000020. doi: 10.1371/journal.pgen.1000020.

    PubMed 18454195

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ORC-13661 in people with Ototoxicity, Drug-Induced, run by Kevin Winthrop at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Daniel Bouchat (503-494-2568, johdanie@ohsu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mitigation or Prevention of Ototoxicity (time frame: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05730283, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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