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

• ClinicalTrials.gov Identifier: NCT02603081
• Recruitment Status: Completed
• First Posted: November 11, 2015
• Last Update Posted: March 18, 2021
• Sponsor: Sound Pharmaceuticals, Incorporated
• Information provided by (Responsible Party): Sound Pharmaceuticals, Incorporated

Tracking Information

• First Submitted Date: November 2, 2015
• First Posted Date: November 11, 2015
• Last Update Posted Date: March 18, 2021
• Study Start Date: December 2015
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2015)

Safety and tolerability of SPI-1005 using histories, physical exams, and clinical measures. [ Time Frame: 7 weeks ]

Incidence of of Treatment-Emergent Adverse Events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 10, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate SPI-1005 in Adults With Meniere's Disease
• Official Title: Phase 1b Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of SPI-1005 in Meniere's Disease
• Brief Summary: 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: 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Meniere's Disease

Intervention

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 Name: ebselen

Study Arms

• Placebo Comparator: Placebo
  0 mg SPI-1005 bid po x 21d
  Intervention: Drug: SPI-1005
• Active Comparator: Low dose
  200 mg SPI-1005 bid po x 21d
  Intervention: Drug: SPI-1005
• Active Comparator: Mid dose
  400 mg SPI-1005 bid po x 21d
  Intervention: Drug: SPI-1005
• Active Comparator: High dose
  600 mg SPI-1005 bid po x 21d
  Intervention: Drug: SPI-1005

Publications *

• 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. 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.
• 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. Review.
• 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). pii: 100005. doi: 10.1016/j.xcrm.2020.100005.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2015): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02603081
• Other Study ID Numbers: SPI-1005-151
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sound Pharmaceuticals, Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Sound Pharmaceuticals, Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Jonathan Kil, MD; Sound Pharmaceuticals

• PRS Account: Sound Pharmaceuticals, Incorporated
• Verification Date: March 2021