Otoprotection With SPI-1005 for Prevention of Temporary Auditory Threshold Shift

NCT01444846 | Completed Phase 2 Results DMC

• 1 other identifier: SPI-1005-202
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Exposure to loud sounds can cause hearing loss. The purpose of this research study is to evaluate potential prevention of temporary changes in hearing that may occur after listening to music through an iPod or personal music player. We will measure temporary changes in hearing in subjects who listen to music and take either the study drug, SPI-1005, or a placebo for 4 days. SPI-1005 is a proprietary preparation of ebselen that allows it to be taken by mouth. Ebselen contains the mineral selenium and behaves like Glutathione Peroxidase, an enzyme that helps to rid the body of damaging chemicals caused by loud sounds.

Conditions

Temporary Auditory Threshold Shift

Keywords

Temporary Auditory Threshold Shift; Hearing Loss; Deafness; SPI-1005; Ebselen

Outcome Measures

Primary Outcomes (2)

• Change in Temporary Threshold Shift at 4 kHz--Intent To Treat (ITT) Population

  The primary efficacy analysis was change in air conduction threshold at 4 kHz collected in the ITT Population on the day of sound exposure. Baseline hearing thresholds were collected on Clinic Visit 2 prior to sound exposure and used in calculating the primary efficacy endpoints. Hearing thresholds after sound exposure were collected and compared to baseline threshold to calculate change from baseline. Threshold changes from baseline were determined for each ear, frequency, and post sound time point, then analyzed by Mixed-effects Model Repeated Measures (MMRM) methods using triply repeated measurements for each subject. The MMRM had fixed effects for treatment, ear, frequency, and time, all 2-way interactions and the 3-way interaction treatment by-frequency-by-time plus a random effect for subject nested within treatment.

  15 minutes post Controlled Sound Challenge

• Change in Temporary Threshold Shift at 4 kHz--Per Protocol (PP) Population

  The primary efficacy analysis was change in air conduction threshold at 4 kHz collected in the PP Population on the day of sound exposure. Baseline hearing thresholds were collected on Clinic Visit 2 prior to sound exposure and used in calculating the primary efficacy endpoints. Hearing thresholds after sound exposure were collected and compared to baseline threshold to calculate change from baseline. Threshold changes from baseline were determined for each ear, frequency, and post sound time point, then analyzed by Mixed-effects Model Repeated Measures (MMRM) methods using triply repeated measurements for each subject. The MMRM had fixed effects for treatment, ear, frequency, and time, all 2-way interactions and the 3-way interaction treatment by-frequency-by-time plus a random effect for subject nested within treatment.

  15 minutes post Controlled Sound Challenge

Study Arms (4)

SPI-1005 Low dose

ACTIVE COMPARATOR

200mg SPI-1005, capsule, bid, po, x4d

Drug: SPI-1005 Low dose

SPI-1005 Middle Dose

ACTIVE COMPARATOR

400mg SPI-1005, capsule, bid, po, x4d

Drug: SPI-1005 Middle dose

SPI-1005 High Dose

ACTIVE COMPARATOR

600mg SPI-1005, capsule, bid, po, x4d

Drug: SPI-1005 High dose

Placebo

PLACEBO COMPARATOR

0mg SPI-1005, capsule, bid, po, x4d

Drug: Placebo

Interventions

SPI-1005 Low dose DRUG

Oral capsules, 200 mg ebselen, twice daily, 4 days

Also known as: 200 mg Ebselen

SPI-1005 Low dose

SPI-1005 Middle dose DRUG

Oral capsules, 400 mg ebselen, twice daily, 4 days

Also known as: 400 mg Ebselen

SPI-1005 Middle Dose

SPI-1005 High dose DRUG

Oral capsules, 600 mg ebselen, twice daily, 4 days

Also known as: 600mgEbselen

SPI-1005 High Dose

Placebo DRUG

Oral capsules, 0 mg ebselen, twice daily, 4 days

Also known as: 0 mg Ebselen

Placebo

Eligibility Criteria

• Age: 18 Years - 31 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects at the time of enrollment.
• Each subject will give informed consent to participate in this study and agrees to the treatment protocol.
• Each subject will be interviewed regarding hearing and health to reveal any history of hearing loss, tinnitus, known ear pathology, use of any potentially ototoxic medications (i.e. diuretics, minocycline).
• Non-occupational sound exposure (e.g., concerts, firearms, fireworks, power tools) will be avoided during the 24-hour period preceding baseline testing and throughout the duration of the study.
• Subjects will have vital signs (i.e., heart rate, blood pressure, respirations, temperature) within normal limits upon medical examination.
• Subjects must have normal audiologic assessment at baseline consisting of:
• Baseline audiometric evaluation confirms that subjects have symmetric hearing with air conduction thresholds no worse than 25 decibels of Hearing Loss (dBHL) at frequencies between 0.25 to 8 kilo Hertz (kHz) bilaterally.
• No significant threshold asymmetry (i.e. greater than 15 dB) between the ears at any tested frequency.
• No significant air-bone gaps (i.e. greater than 10 dB)
• Type A tympanograms bilaterally, defined as a range of -140 to +40 dekaPascals (daPa) based on the 90% range for adults (Margolis and Hunter 2000)

You may not qualify if:

• Subjects with abnormal hearing levels \> 25 dBHL at any tested frequency (250, 500, 1000, 2000, 3000, 4000, 6000 and 8000 Hz) for either ear.
• Exposure to any duration of non-occupational high-level sound (e.g., concerts, firearms, fireworks, power tools) during the 24 hour period preceding baseline audiometric testing as revealed in the subject questionnaire or during the medical examination.
• Pathology of the external ear discovered upon otoscopic examination.
• Pathology of the middle ear revealed by otoscopic examination, abnormal tympanometry, or reported history of middle ear problems.
• Pathology of the inner ear or auditory nerve as revealed by reported history.
• Subject complaints of aural pain, pressure, fullness, or drainage.
• Subjects testing positive for pregnancy will be excluded from the study.
• Subjects with other medical/health issues that would preclude voluntary participation in a drug study may be excluded at the discretion of the Principal Investigator.
• Subjects that have previously received any known potentially ototoxic medication. This includes, but is not limited to, high dose salicylates (\>2 g/day), platinum-based chemotherapeutics and aminoglycoside antibiotics, such as streptomycin, gentamicin,tobramycin, amikacin, neomycin, and netilmycin.
• Subjects that are currently using of any potentially ototoxic medications (i.e. diuretics or minocycline).
• Subjects that have received any investigational treatment (drug or device) in the six months prior to this study.
• Subjects exhibiting or self-reporting shortness of breath, wheezing, coughing, or hemoptysis

Sponsors & Collaborators

• Sound Pharmaceuticals, Incorporated: lead
• University of Florida: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (11)

• Pourbakht A, Yamasoba T. Ebselen attenuates cochlear damage caused by acoustic trauma. Hear Res. 2003 Jul;181(1-2):100-8. doi: 10.1016/s0378-5955(03)00178-3.

  PMID: 12855368 BACKGROUND

• Lynch ED, Gu R, Pierce C, Kil J. Ebselen-mediated protection from single and repeated noise exposure in rat. Laryngoscope. 2004 Feb;114(2):333-7. doi: 10.1097/00005537-200402000-00029.

  PMID: 14755214 BACKGROUND

• Lynch ED, Gu R, Pierce C, Kil J. Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res. 2005 Mar;201(1-2):81-9. doi: 10.1016/j.heares.2004.08.002.

  PMID: 15721563 BACKGROUND

• Yamasoba T, Pourbakht A, Sakamoto T, Suzuki M. Ebselen prevents noise-induced excitotoxicity and temporary threshold shift. Neurosci Lett. 2005 Jun 3;380(3):234-8. doi: 10.1016/j.neulet.2005.01.047. Epub 2005 Feb 1.

  PMID: 15862892 BACKGROUND

• Lynch ED, Kil J. Compounds for the prevention and treatment of noise-induced hearing loss. Drug Discov Today. 2005 Oct 1;10(19):1291-8. doi: 10.1016/S1359-6446(05)03561-0.

  PMID: 16214673 BACKGROUND

• Kil J, Pierce C, Tran H, Gu R, Lynch ED. Ebselen treatment reduces noise induced hearing loss via the mimicry and induction of glutathione peroxidase. Hear Res. 2007 Apr;226(1-2):44-51. doi: 10.1016/j.heares.2006.08.006. Epub 2006 Oct 6.

  PMID: 17030476 BACKGROUND

• Lynch E, Kil J. Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss. Semin Hear 2009; 30(1): 047-055

  BACKGROUND

• Le Prell CG, Yang Q, Harris JG. Modification of digital music files for use in human temporary threshold shift studies. J Acoust Soc Am. 2011 Oct;130(4):EL142-6. doi: 10.1121/1.3630017.

  PMID: 21974483 BACKGROUND

• Le Prell CG, Dell S, Hensley B, Hall JW 3rd, Campbell KC, Antonelli PJ, Green GE, Miller JM, Guire K. Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects. Ear Hear. 2012 Nov-Dec;33(6):e44-58. doi: 10.1097/AUD.0b013e31825f9d89.

  PMID: 22885407 BACKGROUND

• Kil J, Lobarinas E, Spankovich C, Griffiths SK, Antonelli PJ, Lynch ED, Le Prell CG. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2017 Sep 2;390(10098):969-979. doi: 10.1016/S0140-6736(17)31791-9. Epub 2017 Jul 14.

  PMID: 28716314 DERIVED

• Spankovich C, Le Prell CG. Associations between dietary quality, noise, and hearing: data from the National Health and Nutrition Examination Survey, 1999-2002. Int J Audiol. 2014 Nov;53(11):796-809. doi: 10.3109/14992027.2014.921340. Epub 2014 Jun 30.

  PMID: 24975234 DERIVED

MeSH Terms

Conditions

Hearing Loss; Deafness

Interventions

ebselen

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The primary limitations of this study are small sample size and results from a single center. The data collected is supportive of continued evaluation of SPI-1005 for prevention of Temporary Auditory Threshold shift in larger multi-center trials.

Results Point of Contact

• Title: Dr. Jonathan Kil, Chief Medical Officer
• Organization: SOUND PHARMACEUTICALS, INC.

jkil@soundpharma.com

2066342559

Study Officials

• Colleen Le Prell, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Jonathan Kil, MD

  Sound Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: October 3, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: June 3, 2026
• Results First Posted: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)