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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Distortion Product Otoacoustic Emissions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
SPI-1000 Capsule 0mg Ebselen Placebo
0mg Ebselen SPI-1000 bid po x 21d
干预措施: Placebo (Drug)
SPI-1005 Ebselen 200mg Capsule x1
200mg SPI-1005 bid po x 21d Low Dose Arm
干预措施: SPI-1005 Ebselen 200mg Capsule x1 (Drug)
SPI-1005 Ebselen 200mg Capsule x2
400mg SPI-1005 bid po x 21d Mid Dose Arm
干预措施: SPI-1005 Ebselen 200mg Capsule x2 (Drug)
SPI-1005 Ebselen 200mg Capsule x3
600mg SPI-1005 bid po x 21d High Dose Arm
干预措施: SPI-1005 Ebselen 200mg Capsule x3 (Drug)
结局指标
主要结局
Distortion Product Otoacoustic Emissions
时间窗: 7 weeks
Changes in hearing thresholds using pure-tone audiometry with extended high frequency testing
Vertigo severity
时间窗: 7 weeks
vertigo symptom scale
Trough Level of SPI-1005 at 200, 400, and 600 mg Ebselen po bid x 21d
时间窗: 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
时间窗: 7 weeks
Determination of sensorineural hearing loss using pure-tone audiometry
Speech discrimination
时间窗: 7 weeks
Change in Words in noise test (WINT) score
Tinnitus severity
时间窗: 7 weeks
Changes in Tinnitus Functional Index (TFI) score
Changes in lung function
时间窗: 7 weeks
Evaluation of lung function using FEV1
次要结局
- Pharmacodynamics of Nrf2(5 weeks)
- Pharmacodynamics of Glutathione, cysteine and cystine(5 weeks)
- Pharmacogenomics(5 weeks)