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

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

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.

Study Overview

• Status: Completed
• Conditions: Meniere's Disease
• Intervention / Treatment: Drug: SPI-1005

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • House Clinic
  • New York
    • New York, New York, United States, 10028
      • New York Otology
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC
  • Washington
    • Seattle, Washington, United States, 98103
      • Sound Pharmaceuticals, Inc.
    • Seattle, Washington, United States, 98104
      • Northwest Ear

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 0 mg SPI-1005 bid po x 21d	Drug: SPI-1005; 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.; Other Names: ebselen
Active Comparator: Low dose; 200 mg SPI-1005 bid po x 21d	Drug: SPI-1005; 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.; Other Names: ebselen
Active Comparator: Mid dose; 400 mg SPI-1005 bid po x 21d	Drug: SPI-1005; 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.; Other Names: ebselen
Active Comparator: High dose; 600 mg SPI-1005 bid po x 21d	Drug: SPI-1005; 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.; Other Names: ebselen

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sound Pharmaceuticals, Incorporated
• Investigators: Study Chair: Jonathan Kil, MD, Sound Pharmaceuticals

Publications and helpful links

General Publications

• Garland M, Hryckowian AJ, Tholen M, Bender KO, Van Treuren WW, Loscher S, Sonnenburg JL, Bogyo M. The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI. Cell Rep Med. 2020 Apr 21;1(1):100005. doi: 10.1016/j.xcrm.2020.100005.
• Kil J, Harruff EE, Longenecker RJ. Development of ebselen for the treatment of sensorineural hearing loss and tinnitus. Hear Res. 2022 Jan;413:108209. doi: 10.1016/j.heares.2021.108209. Epub 2021 Feb 19.
• 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.
• 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):47-55.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: November 2, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: vertigo; tinnitus; hearing loss; ebselen; Meniere's
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Endolymphatic Hydrops; Meniere Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents; Anti-Ulcer Agents; Antioxidants; Ebselen
• Other Study ID Numbers: SPI-1005-151