Meniere's Disease
Conditions
Keywords
Meniere's disease, Hearing Loss, Vertigo, Tinnitus, Ebselen, Pharmacokinetics, Safety, Efficacy, Speech
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.
Interventions
DRUG200mg SPI-1005 BID
Active: low dose
DRUG400mg SPI-1005 BID
Active: high dose
OTHERPlacebo
Placebo Comparator
Sponsors
Sound Pharmaceuticals, Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
DOUBLE-BLIND
Intervention model description
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) | 8 weeks | 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 | 8 weeks | Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry |
| Efficacy of SPI-1005 on Word Recognition Score | 8 weeks | 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 | 8 weeks | 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 | 8 weeks | 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 | 8 weeks | Improvement in Vertigo Symptom Scale (VSS) from baseline. VSS Total Scale: 0-60, in which a higher score means a worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Plasma Concentration of SPI-1005 | 2 weeks, 4 weeks, 8 weeks | Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals |
Countries
United States
Participant flow
Pre-assignment details
Participants underwent screening procedures, including audiometric evaluation, to ensure they met inclusion/exclusion criteria prior to assignment to a treatment group. 20 patients were screen failures due to not meeting specific inclusion/exclusion criteria. 3 patients were eligible for the study and were assigned to an arm/group but did not start treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo
Placebo: Placebo Comparator | 42 |
| 200mg SPI-1005 Twice Daily (BID) 200mg SPI-1005 BID
200mg SPI-1005 BID: Active: low dose | 42 |
| 400mg SPI-1005 BID 400mg SPI-1005 BID
400mg SPI-1005 BID: Active: high dose | 42 |
| Total | 126 |
Baseline characteristics
| Characteristic | Placebo | Total | 400mg SPI-1005 BID | 200mg SPI-1005 Twice Daily (BID) |
|---|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 13.03 | 53.9 years STANDARD_DEVIATION 11.3 | 50.6 years STANDARD_DEVIATION 10.55 | 55.9 years STANDARD_DEVIATION 9.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 14 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 112 Participants | 38 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 39 Participants | 115 Participants | 39 Participants | 37 Participants |
| Region of Enrollment United States | 42 participants | 126 participants | 42 participants | 42 participants |
| Sex: Female, Male Female | 20 Participants | 66 Participants | 20 Participants | 26 Participants |
| Sex: Female, Male Male | 22 Participants | 60 Participants | 22 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 | 0 / 42 |
| other Total, other adverse events | 3 / 42 | 7 / 42 | 8 / 42 |
| serious Total, serious adverse events | 0 / 42 | 0 / 42 | 0 / 42 |
Outcome results
Primary
Efficacy of SPI-1005 on Hearing Loss
Improvement in sensorineural hearing loss from baseline using Pure Tone Audiometry
Time frame: 8 weeks
Population: Analysis population includes those participants who completed the outcome measure at baseline and 8-week follow-up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | Yes | 15 Participants |
| Placebo | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | No | 26 Participants |
| Placebo | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | Yes | 8 Participants |
| Placebo | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | No | 33 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | No | 35 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | Yes | 16 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | Yes | 7 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | No | 26 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | No | 25 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | No | 16 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement >=10 dB in 2 adjacent low frequencies (250 and 500 Hz, or 500 and 1000 Hz) | Yes | 15 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Hearing Loss | Threshold Improvement from Baseline >=10 dB in at least 1 low frequency (250, 500, or 1000 Hz) | Yes | 25 Participants |
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.
Time frame: 8 weeks
Population: Analysis population includes those participants who completed the outcome measure at baseline and 8-week follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Efficacy of SPI-1005 on Tinnitus | TFI Total Score >= 10pt. reduction from Baseline | 20 Participants |
| Placebo | Efficacy of SPI-1005 on Tinnitus | No TFI Total Score >= 10pt. reduction from Baseline | 21 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Tinnitus | TFI Total Score >= 10pt. reduction from Baseline | 19 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Tinnitus | No TFI Total Score >= 10pt. reduction from Baseline | 23 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Tinnitus | TFI Total Score >= 10pt. reduction from Baseline | 13 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Tinnitus | No TFI Total Score >= 10pt. reduction from Baseline | 28 Participants |
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.
Time frame: 8 weeks
Population: Analysis population includes those participants who completed the outcome measure at baseline and 8-week follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Efficacy of SPI-1005 on Tinnitus Loudness | TL >= 2pt. reduction from Baseline | 14 Participants |
| Placebo | Efficacy of SPI-1005 on Tinnitus Loudness | No TL >= 2pt. reduction from Baseline | 27 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Tinnitus Loudness | TL >= 2pt. reduction from Baseline | 15 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Tinnitus Loudness | No TL >= 2pt. reduction from Baseline | 27 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Tinnitus Loudness | TL >= 2pt. reduction from Baseline | 14 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Tinnitus Loudness | No TL >= 2pt. reduction from Baseline | 27 Participants |
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
Time frame: 8 weeks
Population: Analysis population includes those participants who completed the outcome measure at baseline and 8-week follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Efficacy of SPI-1005 on Vertigo | VSS Total Scale >= 6pt. reduction from Baseline | 21 Participants |
| Placebo | Efficacy of SPI-1005 on Vertigo | No VSS Total Scale >= 6pt. reduction from Baseline | 20 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Vertigo | VSS Total Scale >= 6pt. reduction from Baseline | 21 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Vertigo | No VSS Total Scale >= 6pt. reduction from Baseline | 21 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Vertigo | VSS Total Scale >= 6pt. reduction from Baseline | 18 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Vertigo | No VSS Total Scale >= 6pt. reduction from Baseline | 23 Participants |
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.
Time frame: 8 weeks
Population: Analysis population includes those participants who completed the outcome measure at baseline and 8-week follow-up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | Yes | 23 Participants |
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | No | 18 Participants |
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | Yes | 19 Participants |
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | No | 22 Participants |
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | Yes | 14 Participants |
| Placebo | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | No | 27 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | No | 28 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | Yes | 23 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | No | 24 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | Yes | 13 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | No | 18 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | Yes | 17 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | No | 10 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | Yes | 27 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | No | 16 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=20% | No | 13 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >=10% | Yes | 30 Participants |
| 400mg SPI-1005 BID | Efficacy of SPI-1005 on Word Recognition Score | WIN Score Improvement from Baseline >= 4 words | Yes | 24 Participants |
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.
Time frame: 8 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total Number of Patients with Treatment Emergent Adverse Events (TEAE) | 19 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Mild TEAE | 15 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Moderate TEAE | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Severe TEAE | 0 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Severe TEAE | 0 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total Number of Patients with Treatment Emergent Adverse Events (TEAE) | 20 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Moderate TEAE | 3 Participants |
| 200mg SPI-1005 Twice Daily (BID) | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Mild TEAE | 18 Participants |
| 400mg SPI-1005 BID | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Severe TEAE | 2 Participants |
| 400mg SPI-1005 BID | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Mild TEAE | 18 Participants |
| 400mg SPI-1005 BID | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Number of Patients with Moderate TEAE | 7 Participants |
| 400mg SPI-1005 BID | Number of Participants With Treatment Emergent Adverse Events (TEAE) | Total Number of Patients with Treatment Emergent Adverse Events (TEAE) | 20 Participants |
Secondary
Trough Plasma Concentration of SPI-1005
Trough plasma concentration of SPI-1005 (ebselen) will be determined at certain time intervals
Time frame: 2 weeks, 4 weeks, 8 weeks
Population: In the placebo group, all ebselen concentrations were below the limit of quantitation at all timepoints studied. Therefore, the Analysis Population only includes the SPI-1005 groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough Plasma Concentration of SPI-1005 | 4 weeks | 19.7 ng/mL | Standard Deviation 14.7 |
| Placebo | Trough Plasma Concentration of SPI-1005 | 8 weeks | 0 ng/mL | Standard Deviation 0 |
| Placebo | Trough Plasma Concentration of SPI-1005 | 2 weeks | 27.2 ng/mL | Standard Deviation 19.8 |
| 200mg SPI-1005 Twice Daily (BID) | Trough Plasma Concentration of SPI-1005 | 2 weeks | 48.4 ng/mL | Standard Deviation 33.2 |
| 200mg SPI-1005 Twice Daily (BID) | Trough Plasma Concentration of SPI-1005 | 4 weeks | 40.6 ng/mL | Standard Deviation 29.1 |
| 200mg SPI-1005 Twice Daily (BID) | Trough Plasma Concentration of SPI-1005 | 8 weeks | 0 ng/mL | Standard Deviation 0 |