Clinical trial NCT03325790: SPI-1005 for the Treatment of Patients With Meniere's Disease
Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy of SPI-1005 in Meniere's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Meniere's Disease
Keywords: Meniere's disease
Hearing Loss
Vertigo
Tinnitus
Ebselen
Pharmacokinetics
Safety
Efficacy
Speech
Lead sponsor: Sound Pharmaceuticals, Incorporated
Sponsor class: INDUSTRY
First posted: 2017-10-30
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: 8 weeks
measure: Efficacy of SPI-1005 on Hearing Loss
timeFrame: 8 weeks
measure: Efficacy of SPI-1005 on Word Recognition Score
timeFrame: 8 weeks
measure: Efficacy of SPI-1005 on Tinnitus
timeFrame: 8 weeks
measure: Efficacy of SPI-1005 on Tinnitus Loudness
timeFrame: 8 weeks
measure: Efficacy of SPI-1005 on Vertigo
timeFrame: 8 weeks
Secondary outcomes:
measure: Trough Plasma Concentration of SPI-1005
timeFrame: 2 weeks, 4 weeks, 8 weeks
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Ccent/Cccr
state: California
city: San Diego
country: United States
facility: UCSD
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Miami
country: United States
facility: UMiami
state: Florida
city: Kansas City
country: United States
facility: KUMC
state: Kansas
city: Louisville
country: United States
facility: Advanced ENT & Allergy
state: Kentucky
city: New York
country: United States
facility: ENT and Allergy Associates, LLP
state: New York
city: Charlotte
country: United States
facility: CEENTA
state: North Carolina
city: Philadelphia
country: United States
facility: TJU
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Seattle
country: United States
facility: Northwest Ear, Inc.
state: Washington
Study officials:
affiliation: Sound Pharmaceuticals, Inc.
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, Lobarinas E, Spankovich C, Griffiths SK, Antonelli PJ, Lynch ED, Le Prell CG. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2017 Sep 2;390(10098):969-979. doi: 10.1016/S0140-6736(17)31791-9. Epub 2017 Jul 14.
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: Nelson L, Johns JD, Gu S, Hoa M. Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea. Otol Neurotol. 2021 Dec 1;42(10):e1410-e1421. doi: 10.1097/MAO.0000000000003356.