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

NCT ID: NCT03325790

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2019-04-30

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.

Conditions

Meniere's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo Comparator

200mg SPI-1005 twice daily (BID)

200mg SPI-1005 BID

Group Type: EXPERIMENTAL

200mg SPI-1005 BID

Intervention Type: DRUG

Active: low dose

400mg SPI-1005 BID

400mg SPI-1005 BID

Group Type: EXPERIMENTAL

400mg SPI-1005 BID

Intervention Type: DRUG

Active: high dose

Interventions

200mg SPI-1005 BID

Active: low dose

Intervention Type: DRUG

400mg SPI-1005 BID

Active: high dose

Intervention Type: DRUG

Placebo

Placebo Comparator

Intervention Type: OTHER

Other Intervention Names

ebselen; ebselen

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sound Pharmaceuticals, Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Kil, MD

Role: STUDY_CHAIR

Sound Pharmaceuticals, Inc.

Locations

Ccent/Cccr

Fresno, California, United States

UCSD

San Diego, California, United States

UCSF

San Francisco, California, United States

Georgetown University

Washington D.C., District of Columbia, United States

UMiami

Miami, Florida, United States

KUMC

Kansas City, Kansas, United States

Advanced ENT & Allergy

Louisville, Kentucky, United States

ENT and Allergy Associates, LLP

New York, New York, United States

CEENTA

Charlotte, North Carolina, United States

TJU

Philadelphia, Pennsylvania, United States

MUSC

Charleston, South Carolina, United States

UT Southwestern

Dallas, Texas, United States

Northwest Ear, Inc.

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 17030476 (View on PubMed)

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

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 28716314 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33678494 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34510123 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.soundpharma.com

Sound Pharmaceuticals, Inc.

Other Identifiers

SPI-1005-251

Identifier Type: -

Identifier Source: org_study_id