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SPI-1005 for Prevention and Treatment of Aminoglycoside Induced Ototoxicity

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2016 by Sound Pharmaceuticals, Incorporated
Sponsor:
Collaborators:
Medical University of South Carolina
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Sound Pharmaceuticals, Incorporated
ClinicalTrials.gov Identifier:
NCT02819856
First received: June 16, 2016
Last updated: June 27, 2016
Last verified: June 2016
  Purpose

The primary objective of this study is to determine the safety and tolerability of SPI-1005 treatment in CF patients with active pulmonary exacerbation that are receiving an IV course of tobramycin, using histories, physical exams, vital signs (VS), adverse event (AE) reporting, hematology (CBC) chemistry (Chem-20).

The secondary objectives of this study are to determine the pharmacokinetics of oral SPI-1005 at 200, 400 and 600 mg BID for 14 days. Peak/trough assessments will be determined for ebselen, its major metabolite and selenium. Clinical assessments of the severity of sensorineural hearing loss, speech discrimination, vertigo severity, tinnitus severity and lung function will be made compared between treatment arms and the placebo arm of this study.


Condition Intervention Phase
Ototoxicity
Drug: Placebo
Drug: SPI-1005 Ebselen 200mg Capsule x1
Drug: SPI-1005 Ebselen 200mg Capsule x2
Drug: SPI-1005 Ebselen 200mg Capsule x3
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 1b, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS and PHARMACODYNAMICS OF SPI-1005 in CYSTIC FIBROSIS (CF) PATIENTS WITH ACTIVE PULMONARY EXACERBATION RECEIVING IV TOBRAMYCIN

Resource links provided by NLM:


Further study details as provided by Sound Pharmaceuticals, Incorporated:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 7 weeks ]
    The primary objective of this study is to evaluate the safety and tolerability of SPI-1005 at three different dose levels (200mg, 400mg, and 600mg).


Secondary Outcome Measures:
  • Severity of sensorineural hearing loss [ Time Frame: 7 weeks ]
    Changes in hearing thresholds using pure-tone audiometry with extended high frequency testing

  • Speech discrimination [ Time Frame: 7 weeks ]
    Change in Words in noise test (WINT) score

  • Tinnitus severity [ Time Frame: 7 weeks ]
    Changes in Tinnitus Functional Index (TFI) score

  • Vertigo severity [ Time Frame: 7 weeks ]
    vertigo symptom scale

  • Changes in lung function [ Time Frame: 7 weeks ]
    Evaluation of lung function using FEV1

  • Trough Level of SPI-1005 at 200, 400, and 600 mg Ebselen po bid x 14d [ Time Frame: 7 weeks ]
    Plasma ebselen and major metabolite quantified in plasma by LC-MS/MS


Estimated Enrollment: 80
Study Start Date: August 2016
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: SPI-1000 Capsule 0mg Ebselen Placebo
0mg Ebselen SPI-1000 bid po x 14d
Drug: Placebo
0 mg SPI-1005 bid po x 14d
Other Name: SPI-1000
Experimental: SPI-1005 Ebselen 200mg Capsule x1
200mg SPI-1005 bid po x 14d Low Dose Arm
Drug: SPI-1005 Ebselen 200mg Capsule x1
200 mg SPI-1005 bid po x14d
Other Name: SPI-1005 Low Dose
Experimental: SPI-1005 Ebselen 200mg Capsule x2
400mg SPI-1005 bid po x 14d Mid Dose Arm
Drug: SPI-1005 Ebselen 200mg Capsule x2
400 mg SPI-1005 bid po x 14d
Other Name: SPI-1005 Mid Dose
Experimental: SPI-1005 Ebselen 200mg Capsule x3
600mg SPI-1005 bid po x 14d High Dose Arm
Drug: SPI-1005 Ebselen 200mg Capsule x3
600 mg SPI-1005 bid po x 14d
Other Name: SPI-1005 High Dose

Detailed Description:
Randomized, double-blind, placebo-controlled, dose-escalating, safety, PK, and PD study of oral SPI-1005 in CF patients with active pulmonary exacerbation about to receive a 14-day course of IV tobramycin (10 mg/kg/d). 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 14-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.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 90 days prior to study enrollment.
  • Female patients who are pregnant or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02819856

Contacts
Contact: Jonathan Kil, MD (206) 634- 2559 jkil@soundpharma.com
Contact: Eric D Lynch, PhD 2066342559 elynch@soundpharma.com

Sponsors and Collaborators
Sound Pharmaceuticals, Incorporated
Medical University of South Carolina
Cystic Fibrosis Foundation Therapeutics
Investigators
Study Chair: Jonathan Kil, MD SOUND PHARMACEUTICALS, INC.
  More Information

Publications:
Responsible Party: Sound Pharmaceuticals, Incorporated
ClinicalTrials.gov Identifier: NCT02819856     History of Changes
Other Study ID Numbers: SPI-3005-501
Study First Received: June 16, 2016
Last Updated: June 27, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Ebselen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Neuroprotective Agents

ClinicalTrials.gov processed this record on April 26, 2017