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

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2 Study of the Safety and Efficacy of an Oral Formulation of SPI-1005 for Prevention of Temporary Auditory Threshold Shift

Conditions
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Temporary Auditory Threshold Shift

Intervention / Treatment
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* Drug: SPI-1005 Low dose
* Drug: SPI-1005 Middle dose
* Drug: SPI-1005 High dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: • 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 31 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPI-1005 Low dose<br>200mg SPI-1005, capsule, bid, po, x4d | Drug: SPI-1005 Low dose<br>* Oral capsules, 200 mg ebselen, twice daily, 4 days<br>* Other names: 200 mg Ebselen;|
| Active Comparator: SPI-1005 Middle Dose<br>400mg SPI-1005, capsule, bid, po, x4d | Drug: SPI-1005 Middle dose<br>* Oral capsules, 400 mg ebselen, twice daily, 4 days<br>* Other names: 400 mg Ebselen;|
| Active Comparator: SPI-1005 High Dose<br>600mg SPI-1005, capsule, bid, po, x4d | Drug: SPI-1005 High dose<br>* Oral capsules, 600 mg ebselen, twice daily, 4 days<br>* Other names: 600mgEbselen;|
| Placebo Comparator: Placebo<br>0mg SPI-1005, capsule, bid, po, x4d | Drug: Placebo<br>* Oral capsules, 0 mg ebselen, twice daily, 4 days<br>* Other names: 0 mg Ebselen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Temporary Threshold Shift | Post-sound exposure pure tone audiometry will be compared with baseline (i.e., immediately pre-sound exposure) testing to determine group mean level hearing threshold shift changes between treated and placebo groups. | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Temporary Auditory Threshold Shift, Hearing Loss, Deafness, SPI-1005, Ebselen