SPI-1005 for Prevention and Treatment of Tobramycin Induced Ototoxicity

NCT02819856 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: SPI-3005-501
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 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.

Conditions

Ototoxicity

Keywords

Ebselen; Tinnitus; Hearing Loss; Vertigo; Cystic Fibrosis; Pulmonary Exacerbation; Tobramycin; Safety; Pharmacokinetics; Pharmacodynamics; Aminoglycoside; SPI-1005; Efficacy; Pharmacogenomics; Ototoxicity

Outcome Measures

Primary Outcomes (7)

• Number of participants with sensorineural hearing loss as a measure of safety and efficacy of SPI-1005

  Determination of sensorineural hearing loss using pure-tone audiometry

  7 weeks

• Distortion Product Otoacoustic Emissions

  Changes in hearing thresholds using pure-tone audiometry with extended high frequency testing

  7 weeks

• Speech discrimination

  Change in Words in noise test (WINT) score

  7 weeks

• Tinnitus severity

  Changes in Tinnitus Functional Index (TFI) score

  7 weeks

• Vertigo severity

  vertigo symptom scale

  7 weeks

• Changes in lung function

  Evaluation of lung function using FEV1

  7 weeks

• Trough Level of SPI-1005 at 200, 400, and 600 mg Ebselen po bid x 21d

  Plasma ebselen and major metabolite quantified in plasma by LC-MS/MS

  7 weeks

Secondary Outcomes (3)

• Pharmacogenomics

  5 weeks

• Pharmacodynamics of Nrf2

  5 weeks

• Pharmacodynamics of Glutathione, cysteine and cystine

  5 weeks

Study Arms (4)

SPI-1000 Capsule 0mg Ebselen Placebo

PLACEBO COMPARATOR

0mg Ebselen SPI-1000 bid po x 21d

Drug: Placebo

SPI-1005 Ebselen 200mg Capsule x1

EXPERIMENTAL

200mg SPI-1005 bid po x 21d Low Dose Arm

Drug: SPI-1005 Ebselen 200mg Capsule x1

SPI-1005 Ebselen 200mg Capsule x2

EXPERIMENTAL

400mg SPI-1005 bid po x 21d Mid Dose Arm

Drug: SPI-1005 Ebselen 200mg Capsule x2

SPI-1005 Ebselen 200mg Capsule x3

EXPERIMENTAL

600mg SPI-1005 bid po x 21d High Dose Arm

Drug: SPI-1005 Ebselen 200mg Capsule x3

Interventions

Placebo DRUG

0 mg SPI-1005 bid po x 21d

Also known as: SPI-1000

SPI-1000 Capsule 0mg Ebselen Placebo

SPI-1005 Ebselen 200mg Capsule x1 DRUG

200 mg SPI-1005 bid po x21d

Also known as: SPI-1005 Low Dose

SPI-1005 Ebselen 200mg Capsule x1

SPI-1005 Ebselen 200mg Capsule x2 DRUG

400 mg SPI-1005 bid po x 21d

Also known as: SPI-1005 Mid Dose

SPI-1005 Ebselen 200mg Capsule x2

SPI-1005 Ebselen 200mg Capsule x3 DRUG

600 mg SPI-1005 bid po x 21d

Also known as: SPI-1005 High Dose

SPI-1005 Ebselen 200mg Capsule x3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Sound Pharmaceuticals, Incorporated: lead
• Medical University of South Carolina: collaborator
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

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: 10095194 BACKGROUND

• 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.

  PMID: 17030476 BACKGROUND

• Flume 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: 19729669 BACKGROUND

• Gu 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: 32147183 BACKGROUND

• Harruff 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: 33341407 BACKGROUND

MeSH Terms

Conditions

Ototoxicity; Tinnitus; Hearing Loss; Vertigo; Cystic Fibrosis

Interventions

ebselen

Condition Hierarchy (Ancestors)

Ear Diseases; Otorhinolaryngologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Hearing Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Vestibular Diseases; Labyrinth Diseases; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Jonathan Kil, MD

  SOUND PHARMACEUTICALS, INC.

  STUDY CHAIR

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: August 2, 2024

Record last verified: 2024-08

Locations

US (1)