SPI-1005 for Prevention and Treatment of Tobramycin Induced Ototoxicity

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.

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.