OtotoxicityPhase 2NCT02819856
SPI-1005 for Prevention and Treatment of Tobramycin Induced Ototoxicity
A Phase 2 study testing SPI-1005 Ebselen 200mg Capsule x1, SPI-1005 Ebselen 200mg Capsule x2 and SPI-1005 Ebselen 200mg Capsule x3 in people with Ototoxicity, run by Sound Pharmaceuticals, Incorporated at 1 site in United States.
Trial summary
The primary objective of this study is to determine the safety and efficacy of SPI-1005 treatment in CF patients with active pulmonary exacerbation that are receiving an IV course of tobramycin, determined by comparing hearing assessments, spirometry, Pharmacokinetic (PK), Physical Exam, Adverse Events (AEs) and Labs… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ototoxicity
- What is being tested?
- SPI-1005 Ebselen 200mg Capsule x1, SPI-1005 Ebselen 200mg Capsule x2 and SPI-1005 Ebselen 200mg Capsule x3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2017to 7 Apr 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cystic fibrosis patients about to receive IV tobramycin for acute pulmonary exacerbation.
- Voluntarily consent to participate in the study.
- Females of childbearing potential should be using and committed to continue using one of the following acceptable birth control methods:
- Sexual abstinence (inactivity) for 14 days prior to screening through study completion; or IUD in place for at least 3 months prior to study through study completion; 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 through study completion.
- Ability to perform all behavioral tests as indicated.
Who cannot join
- Current use or within 60 days prior to study enrollment the following IV ototoxic medications: aminoglycoside antibiotics (gentamicin, tobramycin, amikacin, streptomycin); platinum-containing chemotherapies (cisplatin, carboplatin, oxaliplatin); or loop diuretic (furosemide).
- History of idiopathic sensorineural hearing loss, otosclerosis, or vestibular schwannoma.
- History of middle ear or inner ear surgery.
- Current conductive hearing loss or middle ear effusion.
- Significant cardiovascular, hepatic, renal, hematologic, endocrine, immunologic, or psychiatric disease.
- History of hypersensitivity or idiosyncratic reaction to compounds related to ebselen.
- Participation in another investigational drug or device study within 30 days prior to study enrollment.
- Female patients who are pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SPI-1005 in Cystic Fibrosis (CF) Patients With Acute Pulmonary Exacerbation (APE) Receiving IV Tobramycin at Risk for Ototoxicity
The primary objective of this study is to determine the safety and efficacy of SPI-1005 treatment in CF patients with active pulmonary exacerbation that are receiving an IV course of tobramycin, determined by comparing hearing assessments, spirometry, Pharmacokinetic (PK), Physical Exam, Adverse Events (AEs) and Labs baseline to post-treatment.
The secondary objectives of this study are to determine Pharmacogenomics and Pharmacodynamics of SPI-1005.
Read the detailed description
Randomized, double-blind, placebo-controlled study to evaluate the safety, and efficacy of SPI-1005 in Cystic Fibrosis patients with Acute Pulmonary Exacerbation receiving intravenous tobramycin at risk for ototoxicity. All patients will undergo baseline testing and have their severity of lung function, sensorineural hearing loss, tinnitus and vertigo determined before the start of SPI-1005 treatment. SPI-1005 treatment will start within first two days of IV tobramycin treatment and be administered concomitantly. At the end of the 21-day course of SPI-1005 and 28 days following the cessation of SPI-1005, patients will have their hearing loss, tinnitus and vertigo reassessed. Assessments may also include additional audiometric and pulmonary testing, and additional follow-up testing.
- Conditions
- Ototoxicity
- Being tested
- Placebo, SPI-1005 Ebselen 200mg Capsule x1, SPI-1005 Ebselen 200mg Capsule x2, SPI-1005 Ebselen 200mg Capsule x3
- Keywords
- Ebselen, Tinnitus, Hearing Loss, Vertigo, Cystic Fibrosis, Pulmonary Exacerbation, Tobramycin, Safety, Pharmacokinetics, Pharmacodynamics, Aminoglycoside, SPI-1005, Efficacy, Pharmacogenomics, Ototoxicity
- Medical subject headings
- Ototoxicity, Tinnitus, Hearing Loss, Vertigo, Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called SPI-1000
0 mg SPI-1005 bid po x 21d
SPI-1005 Ebselen 200mg Capsule x1Drug
Also called SPI-1005 Low Dose
200 mg SPI-1005 bid po x21d
SPI-1005 Ebselen 200mg Capsule x2Drug
Also called SPI-1005 Mid Dose
400 mg SPI-1005 bid po x 21d
SPI-1005 Ebselen 200mg Capsule x3Drug
Also called SPI-1005 High Dose
600 mg SPI-1005 bid po x 21d
| Study group | Role | What they receive |
|---|---|---|
| SPI-1000 Capsule 0mg Ebselen Placebo | Placebo comparator | 0mg Ebselen SPI-1000 bid po x 21d Receives: Drug: Placebo |
| SPI-1005 Ebselen 200mg Capsule x1 | Experimental | 200mg SPI-1005 bid po x 21d Low Dose Arm Receives: Drug: SPI-1005 Ebselen 200mg Capsule x1 |
| SPI-1005 Ebselen 200mg Capsule x2 | Experimental | 400mg SPI-1005 bid po x 21d Mid Dose Arm Receives: Drug: SPI-1005 Ebselen 200mg Capsule x2 |
| SPI-1005 Ebselen 200mg Capsule x3 | Experimental | 600mg SPI-1005 bid po x 21d High Dose Arm Receives: Drug: SPI-1005 Ebselen 200mg Capsule x3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensorineural Hearing Loss Using Pure-tone Audiometry
Number of participants with ototoxicity: Sensorineural hearing loss using pure-tone audiometry according to the American Speech-Language-Hearing Association (ASHA) criteria for ototoxicity.
Measured: 4 weeks post-tobramycin
Distortion Product Otoacoustic Emissions
Number of participants with ototoxicity: Decreases in Distortion Product Otoacoustic Emissions (DPOAE), defined as a greater than or equal to 5 dB decrease in DPOAE amplitude in at least one test frequency.
Measured: 4 weeks post-tobramycin
Speech Discrimination
Number of participants with ototoxicity: Decreases in speech discrimination using the Words in Noise test (WIN) score (0-35, where higher scores are a better outcome), defined as a 10% or greater decrease in WIN score from participant's baseline score.
Measured: 4 weeks post-tobramycin
Tinnitus Severity
Number of participants with ototoxicity: Increases in Tinnitus Functional Index (TFI) score (0-100, where higher scores are a worse outcome), defined as an increase of 10 points or more from baseline.
Measured: 4 weeks post-tobramycin
Vertigo Severity
Number of participants with vestibulotoxicity: Increases in Vertigo Symptom Scale - Short Form score (0-60, where higher scores are a worse outcome), defined as an increase of 6 points or more from baseline.
Measured: 4 weeks post-tobramycin
Changes in Lung Function
Evaluation of lung function using spirometry, assessed using the change from baseline in Forced Expiratory Volume in 1 second (FEV1).
Measured: 4 weeks post-tobramycin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start21 Jul 2017
- Primary completion7 Apr 2023
- Study completion7 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for OtotoxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sound Pharmaceuticals, Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medical University of South Carolina, Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Jonathan Kil, MD, Study chair, SOUND PHARMACEUTICALS, INC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02819856
- Sponsor's protocol ID
- SPI-3005-501
- Status last verified
- Jun 2026
- First submitted
- 16 Jun 2016
- Last updated
- 16 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Takumida M, Popa R, Anniko M. Free radicals in the guinea pig inner ear following gentamicin exposure. ORL J Otorhinolaryngol Relat Spec. 1999 Mar-Apr;61(2):63-70. doi: 10.1159/000027643.
PubMed 10095194Kil 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.
PubMed 17030476Flume PA, Mogayzel PJ Jr, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC; Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009 Nov 1;180(9):802-8. doi: 10.1164/rccm.200812-1845PP. Epub 2009 Sep 3.
PubMed 19729669Gu R, Longenecker RJ, Homan J, Kil J. Ebselen attenuates tobramycin-induced ototoxicity in mice. J Cyst Fibros. 2021 Mar;20(2):271-277. doi: 10.1016/j.jcf.2020.02.014. Epub 2020 Mar 5.
PubMed 32147183Harruff EE, Kil J, Ortiz MGT, Dorgan D, Jain R, Poth EA, Fifer RC, Kim YJM, Shoup AG, Flume PA. Ototoxicity in cystic fibrosis patients receiving intravenous tobramycin for acute pulmonary exacerbation: Ototoxicity following tobramycin treatment. J Cyst Fibros. 2021 Mar;20(2):288-294. doi: 10.1016/j.jcf.2020.11.020. Epub 2020 Dec 16.
PubMed 33341407