Clinical trial NCT02603081: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Meniere's Disease
Keywords: Meniere's
hearing loss
vertigo
tinnitus
ebselen
Lead sponsor: Sound Pharmaceuticals, Incorporated
Sponsor class: INDUSTRY
First posted: 2015-11-11
Enrollment: 40
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety and tolerability of SPI-1005 using histories, physical exams, and clinical measures.
timeFrame: 7 weeks
Secondary outcomes:
measure: Plasma Ebselen levels of SPI-1005 before, during, and after 21 days of dosing
timeFrame: 7 weeks
measure: Plasma Selenium levels before, during, and after 21 days of dosing
timeFrame: 7 weeks
measure: Impact on Sensorineural Hearing Loss
timeFrame: 7 weeks
measure: Impact on Speech Discrimination
timeFrame: 7 weeks
measure: Impact on Tinnitus
timeFrame: 7 weeks
measure: Impact on Vertigo
timeFrame: 7 weeks
measure: Pharmacodynamic response
timeFrame: 7 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: House Clinic
state: California
city: New York
country: United States
facility: New York Otology
state: New York
city: Charleston
country: United States
facility: MUSC
state: South Carolina
city: Seattle
country: United States
facility: Sound Pharmaceuticals, Inc.
state: Washington
city: Seattle
country: United States
facility: Northwest Ear
state: Washington
Study officials:
affiliation: Sound Pharmaceuticals
name: Jonathan Kil, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.