A Phase 2b Study of SPI-1005 to Prevent Acute Noise Induced Hearing Loss

Study Overview
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Brief Summary
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SPI-1005 is a novel oral drug that contains a glutathione peroxidase mimetic (ebselen) that will be tested in subjects with a history of NIHL at risk for additional NIHL. The goal of this multi-center Phase 2b study is to determine whether SPI-1005 is effective in reducing an acute NIHL in this affected population. In this Phase 2b study subjects with prior NIHL will be enrolled and exposed to a calibrated sound challenge (CSC) that induces a slight acute NIHL.

Detailed Description
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Randomized, double-blind, placebo-controlled, safety and efficacy study of oral SPI-1005 in adults with Noise Induced Hearing Loss (NIHL). All recruited subjects will have their severity of NIHL determined before the start of SPI-1005 treatment using various hearing tests. Subjects will be enrolled and randomized to either placebo or SPI-1005. Subjects will be dosed with either placebo or SPI-1005 for 7 days, beginning 1 day before an acute NIHL. Subjects will have hearing tests performed before and immediately after a calibrated sound challenge (CSC). Follow-up hearing tests will be performed post-CSC.

Official Title
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A Phase 2b, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of SPI-1005 to Prevent Acute Noise Induced Hearing Loss (PANIHL)

Conditions
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Noise Induced Hearing Loss

Intervention / Treatment
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* Drug: SPI-1005 200mg
* Drug: SPI-1005 400mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female patients, 18-50 years of age History of either recreational and/or occupational exposure to noise Voluntarily consent to participate in the study Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods: Sexual abstinence (inactivity) for 14 days prior to screening through study completion; or intra-uterine device in place for at least 3 months prior to study through study completion; or barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion; or stable hormonal contraceptive for at least 3 months prior to study through study completion; or surgical sterilization (vasectomy) of partner at least 6 months prior to study. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be at least 3 years since last menses. Exclusion Criteria: Current use or within 60 days prior to study of excluded ototoxic medications History of autoimmune inner ear disease History of middle ear or inner ear surgery Current conductive hearing loss or middle ear effusion Significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, or psychiatric disease History of hypersensitivity or idiosyncratic reaction to compounds related to ebselen Current use or within 30 days prior to study of drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes Participation in another investigational drug or device study within 90 days prior to study enrollment Female patients who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPI-1005 200 mg<br>200 mg SPI-1005, capsule, bid, po, x7d | Drug: SPI-1005 200mg<br>* Oral SPI-1005 capsules, 200 mg ebselen, twice daily, 7 days<br>* Other names: Low Dose;|
| Active Comparator: SPI-1005 400 mg<br>400 mg SPI-1005, capsule, bid, po, x7d | Drug: SPI-1005 400mg<br>* Oral SPI-1005 capsules, 400 mg ebselen, twice daily, 7 days<br>* Other names: High Dose;|
| Placebo Comparator: Placebo<br>0 mg SPI-1005, capsule, bid, po, x7d | Drug: Placebo<br>* Oral SPI-1005 capsules, 0 mg ebselen, twice daily, 7 days<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in the Incidence of a Significant Threshold Shift | Post Controlled Sound Challenge pure tone audiometry will be compared with baseline | Within 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in word recognition score | Post Controlled Sound Challenge Words in Noise Test score will be compared with baseline | Within 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Noise Induced Hearing Loss, Prevent Acute Noise Induced Hearing Loss