SPI-1005 for Prevention and Treatment of Tobramycin Induced Ototoxicity

Phase 2

Completed

• Conditions: Ototoxicity
• Interventions: Drug: Placebo; Drug: SPI-1005 Ebselen 200mg Capsule x1; Drug: SPI-1005 Ebselen 200mg Capsule x2; Drug: SPI-1005 Ebselen 200mg Capsule x3

• Registration Number: NCT02819856
• Lead Sponsor: Sound Pharmaceuticals, Incorporated

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.

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.

Study Timeline

• Study First Submitted: 2016-06-16
• Study First Submitted QC: 2016-06-27
• Study First Posted: 2016-06-30
• Study Start: 2017-07-21
• Primary Completion: 2023-04-07
• Study Completion: 2023-04-07
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-01
• Last Update Posted: 2024-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SPI-1000 Capsule 0mg Ebselen Placebo	Placebo	0mg Ebselen SPI-1000 bid po x 21d
SPI-1005 Ebselen 200mg Capsule x1	SPI-1005 Ebselen 200mg Capsule x1	200mg SPI-1005 bid po x 21d Low Dose Arm
SPI-1005 Ebselen 200mg Capsule x2	SPI-1005 Ebselen 200mg Capsule x2	400mg SPI-1005 bid po x 21d Mid Dose Arm
SPI-1005 Ebselen 200mg Capsule x3	SPI-1005 Ebselen 200mg Capsule x3	600mg SPI-1005 bid po x 21d High Dose Arm

Primary Outcome Measures

Name	Time	Method
Distortion Product Otoacoustic Emissions	7 weeks	Changes in hearing thresholds using pure-tone audiometry with extended high frequency testing
Vertigo severity	7 weeks	vertigo symptom scale
Trough Level of SPI-1005 at 200, 400, and 600 mg Ebselen po bid x 21d	7 weeks	Plasma ebselen and major metabolite quantified in plasma by LC-MS/MS
Number of participants with sensorineural hearing loss as a measure of safety and efficacy of SPI-1005	7 weeks	Determination of sensorineural hearing loss using pure-tone audiometry
Speech discrimination	7 weeks	Change in Words in noise test (WINT) score
Tinnitus severity	7 weeks	Changes in Tinnitus Functional Index (TFI) score
Changes in lung function	7 weeks	Evaluation of lung function using FEV1

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics of Nrf2	5 weeks	Explore SPI-1005 on the level of Nrf2 by PCR
Pharmacodynamics of Glutathione, cysteine and cystine	5 weeks	Explore SPI-1005 on the level of Glutathione, cysteine and cystine measured in µM.
Pharmacogenomics	5 weeks	Pharmacogenomics analysis will explore SPI-1005 as an inducer of gene expression for Nrf2, glutathione peroxidase-1, hemeoxygenase-1, and thioredoxin class of redox proteins.

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States