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

Primary Purpose

Meniere's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
200mg SPI-1005 BID
400mg SPI-1005 BID
Placebo
Sponsored by
Sound Pharmaceuticals, Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Meniere's Disease focused on measuring Meniere's disease, Hearing Loss, Vertigo, Tinnitus, Ebselen, Pharmacokinetics, Safety, Efficacy, Speech

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, carboplatinum, 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.

Sites / Locations

  • Ccent/Cccr
  • UCSD
  • UCSF
  • Georgetown University
  • UMiami
  • KUMC
  • Advanced ENT & Allergy
  • ENT and Allergy Associates, LLP
  • CEENTA
  • TJU
  • MUSC
  • UT Southwestern
  • Northwest Ear, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

200mg SPI-1005 twice daily (BID)

400mg SPI-1005 BID

Arm Description

Placebo

200mg SPI-1005 BID

400mg SPI-1005 BID

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAE)
Number and severity of adverse events in patients treated with placebo versus SPI-1005. Outcome Measure 1 includes all adverse events, including those which are not reported in the Adverse Event module, i.e., adverse events which did not result in death, were not Serious Adverse Events, and which were below the frequency threshold (5%) in any arm as required for reporting.
Efficacy of SPI-1005 on Hearing Loss
Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry
Efficacy of SPI-1005 on Word Recognition Score
Improvement in Words-in-Noise (WIN) test score from baseline. WIN test score, 0-35 words, in which a higher score means a better outcome.
Efficacy of SPI-1005 on Tinnitus
Improvement in the Tinnitus Functional Index (TFI) from baseline. TFI Total Score: 0-100, in which a higher score means a worse outcome.
Efficacy of SPI-1005 on Tinnitus Loudness
Improvement in Tinnitus Loudness (TL) on response to Tinnitus Functional Index Question Number 2. Question Number 2: "How Strong or Loud is your tinnitus?": 0-10, in which a higher score means a worse outcome.
Efficacy of SPI-1005 on Vertigo
Improvement in Vertigo Symptom Scale (VSS) from baseline. VSS Total Scale: 0-60, in which a higher score means a worse outcome

Secondary Outcome Measures

Trough Plasma Concentration of SPI-1005
Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals

Full Information

First Posted
October 4, 2017
Last Updated
August 21, 2023
Sponsor
Sound Pharmaceuticals, Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03325790
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 28, 2017 (Actual)
Primary Completion Date
April 30, 2019 (Actual)
Study Completion Date
April 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sound Pharmaceuticals, Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Meniere's Disease
Keywords
Meniere's disease, Hearing Loss, Vertigo, Tinnitus, Ebselen, Pharmacokinetics, Safety, Efficacy, Speech

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
DOUBLE-BLIND
Allocation
Randomized
Enrollment
149 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
200mg SPI-1005 twice daily (BID)
Arm Type
Experimental
Arm Description
200mg SPI-1005 BID
Arm Title
400mg SPI-1005 BID
Arm Type
Experimental
Arm Description
400mg SPI-1005 BID
Intervention Type
Drug
Intervention Name(s)
200mg SPI-1005 BID
Other Intervention Name(s)
ebselen
Intervention Description
Active: low dose
Intervention Type
Drug
Intervention Name(s)
400mg SPI-1005 BID
Other Intervention Name(s)
ebselen
Intervention Description
Active: high dose
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Description
Number and severity of adverse events in patients treated with placebo versus SPI-1005. Outcome Measure 1 includes all adverse events, including those which are not reported in the Adverse Event module, i.e., adverse events which did not result in death, were not Serious Adverse Events, and which were below the frequency threshold (5%) in any arm as required for reporting.
Time Frame
8 weeks
Title
Efficacy of SPI-1005 on Hearing Loss
Description
Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry
Time Frame
8 weeks
Title
Efficacy of SPI-1005 on Word Recognition Score
Description
Improvement in Words-in-Noise (WIN) test score from baseline. WIN test score, 0-35 words, in which a higher score means a better outcome.
Time Frame
8 weeks
Title
Efficacy of SPI-1005 on Tinnitus
Description
Improvement in the Tinnitus Functional Index (TFI) from baseline. TFI Total Score: 0-100, in which a higher score means a worse outcome.
Time Frame
8 weeks
Title
Efficacy of SPI-1005 on Tinnitus Loudness
Description
Improvement in Tinnitus Loudness (TL) on response to Tinnitus Functional Index Question Number 2. Question Number 2: "How Strong or Loud is your tinnitus?": 0-10, in which a higher score means a worse outcome.
Time Frame
8 weeks
Title
Efficacy of SPI-1005 on Vertigo
Description
Improvement in Vertigo Symptom Scale (VSS) from baseline. VSS Total Scale: 0-60, in which a higher score means a worse outcome
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Trough Plasma Concentration of SPI-1005
Description
Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals
Time Frame
2 weeks, 4 weeks, 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Kil, MD
Organizational Affiliation
Sound Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Ccent/Cccr
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
UCSD
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
UMiami
City
Miami
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
KUMC
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Advanced ENT & Allergy
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
ENT and Allergy Associates, LLP
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
CEENTA
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
TJU
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19144
Country
United States
Facility Name
MUSC
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
UT Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Northwest Ear, Inc.
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17030476
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.
Results Reference
background
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
Results Reference
background
PubMed Identifier
28716314
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.
Results Reference
background
PubMed Identifier
33678494
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.
Results Reference
background
PubMed Identifier
34510123
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.
Results Reference
derived
Links:
URL
http://www.soundpharma.com
Description
Sound Pharmaceuticals, Inc.

Learn more about this trial

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

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