SPI-1005 for Prevention and Treatment of Tobramycin Induced Ototoxicity
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
1 other identifier
interventional
35
1 country
1
Brief 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 baseline to post-treatment. The secondary objectives of this study are to determine Pharmacogenomics and Pharmacodynamics of SPI-1005.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2016
CompletedFirst Posted
Study publicly available on registry
June 30, 2016
CompletedStudy Start
First participant enrolled
July 21, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 7, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 7, 2023
CompletedResults Posted
Study results publicly available
June 25, 2026
CompletedJuly 16, 2026
June 1, 2026
5.7 years
June 16, 2016
May 31, 2026
June 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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.
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.
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.
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.
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.
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).
4 weeks post-tobramycin
Study Arms (4)
SPI-1000 Capsule 0mg Ebselen Placebo
PLACEBO COMPARATOR0mg Ebselen SPI-1000 bid po x 21d
SPI-1005 Ebselen 200mg Capsule x1
EXPERIMENTAL200mg SPI-1005 bid po x 21d Low Dose Arm
SPI-1005 Ebselen 200mg Capsule x2
EXPERIMENTAL400mg SPI-1005 bid po x 21d Mid Dose Arm
SPI-1005 Ebselen 200mg Capsule x3
EXPERIMENTAL600mg SPI-1005 bid po x 21d High Dose Arm
Interventions
200 mg SPI-1005 bid po x21d
400 mg SPI-1005 bid po x 21d
600 mg SPI-1005 bid po x 21d
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sound Pharmaceuticals, Incorporatedlead
- Medical University of South Carolinacollaborator
- Cystic Fibrosis Foundationcollaborator
Study Sites (1)
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Related Publications (5)
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.
PMID: 10095194BACKGROUNDKil 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.
PMID: 17030476BACKGROUNDFlume 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.
PMID: 19729669BACKGROUNDGu 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.
PMID: 32147183BACKGROUNDHarruff 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.
PMID: 33341407BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Sound Pharmaceuticals, Inc.
Study Officials
- STUDY CHAIR
Jonathan Kil, MD
SOUND PHARMACEUTICALS, INC.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2016
First Posted
June 30, 2016
Study Start
July 21, 2017
Primary Completion
April 7, 2023
Study Completion
April 7, 2023
Last Updated
July 16, 2026
Results First Posted
June 25, 2026
Record last verified: 2026-06