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

Meniere's Disease Clinical Trial

Official title:

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy of SPI-1005 in Meniere's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03325790
• Other study ID #: SPI-1005-251
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2017
• Est. completion date: April 30, 2019

Study information

• Verified date: August 2023
• Source: Sound Pharmaceuticals, Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Meniere Disease
• Meniere's Disease

Intervention

Drug:
• 200mg SPI-1005 BID
Active: low dose
• 400mg SPI-1005 BID
Active: high dose

Other:
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
United States	MUSC	Charleston	South Carolina
United States	CEENTA	Charlotte	North Carolina
United States	UT Southwestern	Dallas	Texas
United States	Ccent/Cccr	Fresno	California
United States	KUMC	Kansas City	Kansas
United States	Advanced ENT & Allergy	Louisville	Kentucky
United States	UMiami	Miami	Florida
United States	ENT and Allergy Associates, LLP	New York	New York
United States	TJU	Philadelphia	Pennsylvania
United States	UCSD	San Diego	California
United States	UCSF	San Francisco	California
United States	Northwest Ear, Inc.	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sound Pharmaceuticals, Incorporated

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	8 weeks
Primary	Efficacy of SPI-1005 on Hearing Loss	Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry	8 weeks
Primary	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.	8 weeks
Primary	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.	8 weeks
Primary	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.	8 weeks
Primary	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	8 weeks
Secondary	Trough Plasma Concentration of SPI-1005	Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals	2 weeks, 4 weeks, 8 weeks

External Links

•   Sound Pharmaceuticals, Inc.