Study to Evaluate SPI-1005 in Adults With Meniere's Disease

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of three dose levels of SPI-1005 compared to placebo on vertigo, tinnitus and sensorineural hearing loss in 40 adults with Meniere's disease.

Detailed Description
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Randomized, double-blind, placebo-controlled safety, pharmacokinetic, pharmacodynamic study of oral SPI-1005 in adults with Meniere's disease. All subjects will undergo baseline audiometric testing and have their severity of sensorineural hearing loss, tinnitus and vertigo determined before the start of a 21-day course of treatment with SPI-1005 or placebo. During treatment with SPI-1005, and 7 days and 28 days following the cessation of SPI-1005, subjects will have their hearing loss, tinnitus and vertigo assessed. Additional testing including electrocochleography will be performed at baseline, at the end of SPI-1005 treatment, and 28 days after the SPI-1005 treatment has stopped. Six outpatient visits will be performed over a 7-week period.

Official Title
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Phase 1b Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of SPI-1005 in Meniere's Disease

Conditions
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Meniere's Disease

Intervention / Treatment
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* Drug: SPI-1005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of probable or definite Meniere's Disease by AAO-HNS 1995 criteria within 12 months of study enrollment; 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 IUD 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 90 days prior to study of ototoxic medications such as aminoglycoside antibiotics (gentamicin, tobramycin, amikacin, streptomycin); platinum-containing chemotherapies (cisplatin, carboplatin, oxaliplatin); or loop diuretic (furosemide); History of idiopathic sensorineural hearing loss, otosclerosis, or vestibular schwannoma; 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: 19 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>0 mg SPI-1005 bid po x 21d | Drug: SPI-1005<br>* Ebselen is a small molecule mimic and inducer of glutathione peroxidase (GPx). GPx reduces reactive oxygen species by the binding of free radicals to its selenium moiety. Ebselen has strong anti-inflammatory characteristics.<br>* Other names: ebselen;|
| Active Comparator: Low dose<br>200 mg SPI-1005 bid po x 21d | Drug: SPI-1005<br>* Ebselen is a small molecule mimic and inducer of glutathione peroxidase (GPx). GPx reduces reactive oxygen species by the binding of free radicals to its selenium moiety. Ebselen has strong anti-inflammatory characteristics.<br>* Other names: ebselen;|
| Active Comparator: Mid dose<br>400 mg SPI-1005 bid po x 21d | Drug: SPI-1005<br>* Ebselen is a small molecule mimic and inducer of glutathione peroxidase (GPx). GPx reduces reactive oxygen species by the binding of free radicals to its selenium moiety. Ebselen has strong anti-inflammatory characteristics.<br>* Other names: ebselen;|
| Active Comparator: High dose<br>600 mg SPI-1005 bid po x 21d | Drug: SPI-1005<br>* Ebselen is a small molecule mimic and inducer of glutathione peroxidase (GPx). GPx reduces reactive oxygen species by the binding of free radicals to its selenium moiety. Ebselen has strong anti-inflammatory characteristics.<br>* Other names: ebselen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SPI-1005 using histories, physical exams, and clinical measures. | Incidence of of Treatment-Emergent Adverse Events | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Ebselen levels of SPI-1005 before, during, and after 21 days of dosing | Evaluation of potential accumulation of study drug | 7 weeks | 
| Plasma Selenium levels before, during, and after 21 days of dosing | Evaluation of potential changes in plasma selenium levels | 7 weeks | 
| Impact on Sensorineural Hearing Loss | Pure Tone Audiometry | 7 weeks | 
| Impact on Speech Discrimination | Words in Noise Test | 7 weeks | 
| Impact on Tinnitus | Questionnaire | 7 weeks | 
| Impact on Vertigo | Questionnaire | 7 weeks | 
| Pharmacodynamic response | Electrocochleography | 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meniere's, hearing loss, vertigo, tinnitus, ebselen