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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Medical University of South Carolina
Charleston, South Carolina, United States
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
Time frame: 7 weeks
Distortion Product Otoacoustic Emissions
Changes in hearing thresholds using pure-tone audiometry with extended high frequency testing
Time frame: 7 weeks
Speech discrimination
Change in Words in noise test (WINT) score
Time frame: 7 weeks
Tinnitus severity
Changes in Tinnitus Functional Index (TFI) score
Time frame: 7 weeks
Vertigo severity
vertigo symptom scale
Time frame: 7 weeks
Changes in lung function
Evaluation of lung function using FEV1
Time frame: 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
Time frame: 7 weeks
Pharmacogenomics
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.
Time frame: 5 weeks
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600 mg SPI-1005 bid po x 21d
Pharmacodynamics of Nrf2
Explore SPI-1005 on the level of Nrf2 by PCR
Time frame: 5 weeks
Pharmacodynamics of Glutathione, cysteine and cystine
Explore SPI-1005 on the level of Glutathione, cysteine and cystine measured in µM.
Time frame: 5 weeks