SPI-1005 for the Treatment of Patients With Meniere's Disease

Study Overview
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Brief Summary
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This study will evaluate the safety, efficacy, and Pharmacokinetics (PK) of two dose levels of SPI-1005 administered for 28 days compared to placebo in patients with Meniere's disease.

Detailed Description
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Study participants will be randomized to SPI-1005 or placebo in this double-blind study to evaluate both safety and efficacy of the investigational treatment. Participants, aged 18-75 years, with probable or definite Meniere's disease will undergo baseline testing to assess severity of sensorineural hearing loss, tinnitus and vertigo. During the study, and 28 days after completion of treatment, participants will be evaluated for safety (adverse events, physical examinations, vital signs and clinical laboratory testing (CBC,serum chemistry). Trough plasma levels of ebselen and its major metabolite will be determined using liquid chromatography-mass spectrometry (LCMS) at specified visits. Additionally, plasma will be analyzed for selenium at the corresponding visits. The effect of SPI-1005 on hearing and balance will be evaluated. Tinnitus (TFI) and vertigo (VSS) will be evaluated at baseline, during and study treatment.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy of SPI-1005 in Meniere's Disease

Conditions
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Meniere's Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female patients, 18-75 years of age at the time of enrollment. Diagnosis of probable or definitive Meniere's disease by American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) 1995 criteria. Two of three active symptoms including vertigo or disequilibrium, fluctuating hearing loss, or tinnitus within the 3 months prior to study enrollment. Hearing loss of ≥ 30 decibels (dBHL) at either 250, 500 or 1000 Hz. Voluntary consent to participate in the study. Male subjects that are willing to use condoms throughout the study period and 90-days following study completion even if not fertile. Females of childbearing potential should either be sexually inactive (abstinent) for 14 days prior to screening and throughout the study or be using one of the following acceptable birth control methods: Intrauterine Device in place for at least 3 months prior to study; 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 and through study completion; or Surgical sterilization (vasectomy) of partner at least 6 months prior to study enrollment. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study enrollment, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be at least 1 year since last menses. Exclusion Criteria: Current use of or within 60 days prior to study IV ototoxic medications such as chemotherapy including cisplatin, carboplatin, or oxaliplatin; aminoglycoside antibiotics including gentamicin, amikacin, tobramycin, kanamycin, or streptomycin; or loop diuretics including furosemide. History of otosclerosis or vestibular schwannoma. History of significant middle ear or inner ear surgery. Current conductive hearing loss, otitis media, or mixed hearing loss. Significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, or psychiatric disease. Current use or within 30 days prior to study enrollment systemic steroids or drugs known to be strong inhibitors or inducers of cytochrome P450 enzymes. Hypersensitivity or idiosyncratic reaction to compounds related to ebselen or selenium. Female patients who are pregnant or breastfeeding. Participation in another interventional drug or device study within 30 days prior to study consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo Comparator<br>|
| Experimental: 200mg SPI-1005 twice daily (BID)<br>200mg SPI-1005 BID | Drug: 200mg SPI-1005 BID<br>* Active: low dose<br>* Other names: ebselen;|
| Experimental: 400mg SPI-1005 BID<br>400mg SPI-1005 BID | Drug: 400mg SPI-1005 BID<br>* Active: high dose<br>* Other names: ebselen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number and severity of adverse events in patients treated with placebo versus SPI-1005. Outcome Measure 1 includes all adverse events, including those which are not reported in the Adverse Event module, i.e., adverse events which did not result in death, were not Serious Adverse Events, and which were below the frequency threshold (5%) in any arm as required for reporting. | 8 weeks | 
| Efficacy of SPI-1005 on Hearing Loss | Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry | 8 weeks | 
| Efficacy of SPI-1005 on Word Recognition Score | Improvement in Words-in-Noise (WIN) test score from baseline. WIN test score, 0-35 words, in which a higher score means a better outcome. | 8 weeks | 
| Efficacy of SPI-1005 on Tinnitus | Improvement in the Tinnitus Functional Index (TFI) from baseline. TFI Total Score: 0-100, in which a higher score means a worse outcome. | 8 weeks | 
| Efficacy of SPI-1005 on Tinnitus Loudness | Improvement in Tinnitus Loudness (TL) on response to Tinnitus Functional Index Question Number 2. Question Number 2: How Strong or Loud is your tinnitus?: 0-10, in which a higher score means a worse outcome. | 8 weeks | 
| Efficacy of SPI-1005 on Vertigo | Improvement in Vertigo Symptom Scale (VSS) from baseline. VSS Total Scale: 0-60, in which a higher score means a worse outcome | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough Plasma Concentration of SPI-1005 | Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals | 2 weeks, 4 weeks, 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meniere's disease, Hearing Loss, Vertigo, Tinnitus, Ebselen, Pharmacokinetics, Safety, Efficacy, Speech