SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss

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ClinicalTrials.gov Identifier: NCT01451853

Recruitment Status : Unknown

Verified September 2017 by Sound Pharmaceuticals, Incorporated.
Recruitment status was: Not yet recruiting

First Posted : October 14, 2011

Last Update Posted : September 25, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

VA Puget Sound Health Care System

Information provided by (Responsible Party):

Sound Pharmaceuticals, Incorporated

Study Description

Brief Summary:

Chemotherapy treatment with platinum based agents is well noted to cause ototoxicity. It is the objective of this study to determine the safety and efficacy of SPI-1005 at three dose levels when delivered orally twice daily for 3 days, surrounding each cycle of platinum chemotherapy in head and neck or non-small cell lung cancer patients to prevent and treat chemotherapy induced hearing loss and tinnitus.

Condition or disease	Intervention/treatment	Phase
Lung Cancer Head and Neck Cancer Hearing Loss Ototoxicity Tinnitus Neuropathy	Drug: SPI-1005 Low Dose Drug: SPI-1005 Middle Dose Drug: SPI-1005 High Dose Drug: Placebo	Phase 2

Detailed Description:

Chemotherapy treatment with the platinum containing chemotherapies (e.g. cisplatin, carboplatin) are well noted and studied for their ability to cause ototoxicity which includes hearing loss, tinnitus, vertigo, or dizziness. It is the objective of this study to determine the safety and efficacy of SPI-1005 at three dose levels when delivered orally twice daily for 3 days, surrounding each cycle of platinum chemotherapy for head and neck or non-small cell lung cancer patients to prevent and treat chemotherapy induced hearing loss and tinnitus.

SPI-1005, a proprietary oral formulation of ebselen is a small molecule mimic and inducer of the enzyme Glutathione Peroxidase. GPx reduces reactive oxygen species (ROS) by reacting with glutathione. SPI-1005 has been shown to reduce cisplatin induced hearing threshold shift in animal studies.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Safety and Efficacy Study of SPI-1005 for Prevention of Chemotherapy Induced Hearing Loss
Estimated Study Start Date :	January 15, 2018
Estimated Primary Completion Date :	June 26, 2019
Estimated Study Completion Date :	September 23, 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Nonsyndromic hearing loss

MedlinePlus related topics: Hearing Disorders and Deafness

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: SPI-1005 Low Dose 200 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy	Drug: SPI-1005 Low Dose Oral capsules, 200 mg ebselen, twice daily, 3 days for each cycle of chemotherapy Arms: Low Dose Other Names: 200 mg Ebselen Other Name: 200 mg Ebselen
Active Comparator: SPI-1005 Middle Dose 400 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy	Drug: SPI-1005 Middle Dose Oral capsules, 400 mg ebselen, twice daily, 3 days for each cycle of chemotherapy Other Name: 400 mg Ebselen
Active Comparator: SPI-1005 High Dose 600 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy	Drug: SPI-1005 High Dose Oral capsules, 600 mg ebselen, twice daily, 3 days for each cycle of chemotherapy Other Name: 600 mg Ebselen
Placebo Comparator: Placebo 0 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy	Drug: Placebo Oral capsules, 0 mg ebselen, twice daily, 3 days for each cycle of chemotherapy Other Name: 0 mg Ebselen

Outcome Measures

Primary Outcome Measures :

Number of participants with adverse events [ Time Frame: 12 months ]

Secondary Outcome Measures :

Reduction of hearing loss incidence and severity [ Time Frame: From baseline through 1 month after last chemotherapy cycle ]
Reduction of tinnitus incidence and severity. [ Time Frame: From baseline through 1 month after last chemotherapy cycle ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	19 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult male and female subjects, 19-80 years of age;
Confirmed diagnosis of advanced head and neck cancer or advanced lung cancer
Voluntarily consent to participate in the study
Females of childbearing potential should either be sexually inactive (abstinent) for 14 days prior to screening and throughout the study or be using one of the following acceptable birth control methods:
IUD in place for at least 3 months prior to study;
Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion;
Stable hormonal contraceptive for at least 3 months prior to study through completion of study;
Surgical sterilization (vasectomy) of partner at least 6 months prior to study.
Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study, hysterectomy, or bilateral oophorectomy at least 2 months prior to study).

Exclusion Criteria:

Subjects previously treated with chemotherapy, antibiotics, or diuretics known to cause hearing loss in the last 90 days
History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, otologic, or psychiatric disease
Presence of alcoholism or drug abuse
Participation in another investigational drug or device clinical trial within 30 days prior to the study
Female subjects who are pregnant or lactating

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01451853

Contacts

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Contact: Eric Lynch, PhD	(206) 634-2559	elynch@soundpharma.com

Locations

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United States, Washington
VA Puget Sound Health Care
Seattle, Washington, United States, 98108
Contact: Tony S. Quang, M.D. 206-768-5356
Principal Investigator: Tony S Quang, M.D.

Sponsors and Collaborators

Sound Pharmaceuticals, Incorporated

VA Puget Sound Health Care System

Investigators

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Study Director:	Jonathan Kil, MD	Sound Pharmaceuticals, Inc.

More Information

Publications:

Rybak LP, Whitworth C, Somani S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope. 1999 Nov;109(11):1740-4. doi: 10.1097/00005537-199911000-00003.

Rybak LP, Somani S. Ototoxicity. Amelioration by protective agents. Ann N Y Acad Sci. 1999 Nov 28;884:143-51.

Lynch ED, Gu R, Pierce C, Kil J. Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res. 2005 Mar;201(1-2):81-9. doi: 10.1016/j.heares.2004.08.002.

Lynch ED, Gu R, Pierce C, Kil J. Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity. Anticancer Drugs. 2005 Jun;16(5):569-79. doi: 10.1097/00001813-200506000-00013.

Knight KR, Kraemer DF, Winter C, Neuwelt EA. Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol. 2007 Apr 1;25(10):1190-5. doi: 10.1200/JCO.2006.07.9723.

Reavis KM, Phillips DS, Fausti SA, Gordon JS, Helt WJ, Wilmington D, Bratt GW, Konrad-Martin D. Factors affecting sensitivity of distortion-product otoacoustic emissions to ototoxic hearing loss. Ear Hear. 2008 Dec;29(6):875-93. doi: 10.1097/AUD.0b013e318181ad99.

Kim SJ, Park C, Han AL, Youn MJ, Lee JH, Kim Y, Kim ES, Kim HJ, Kim JK, Lee HK, Chung SY, So H, Park R. Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells. Hear Res. 2009 May;251(1-2):70-82. doi: 10.1016/j.heares.2009.03.003. Epub 2009 Mar 13.

Lynch E, Kil J. Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss. Semin Hear 2009; 30(1): 047-055

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Responsible Party:	Sound Pharmaceuticals, Incorporated
ClinicalTrials.gov Identifier:	NCT01451853
Other Study ID Numbers:	SPI-3005-201
First Posted:	October 14, 2011 Key Record Dates
Last Update Posted:	September 25, 2017
Last Verified:	September 2017

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Sound Pharmaceuticals, Incorporated:


Lung Cancer Head and Neck Cancer Hearing Loss Ototoxicity Tinnitus	Deafness SPI-1005 Cisplatin Carboplatin Ebselen

Additional relevant MeSH terms:

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Head and Neck Neoplasms Hearing Loss Deafness Tinnitus Ototoxicity Neoplasms by Site Neoplasms Hearing Disorders Ear Diseases Otorhinolaryngologic Diseases Sensation Disorders Neurologic Manifestations Nervous System Diseases Pathologic Processes Drug-Related Side Effects and Adverse Reactions	Chemically-Induced Disorders Radiation Injuries Wounds and Injuries 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

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