Noise-Induced Hearing Loss-Acute Exposure Treatment

NCT04768569 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PINIHL-AET
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and efficacy of zonisamide for the treatment of noise-induced hearing loss in adults.

Conditions

Hearing Loss, Noise-Induced

Outcome Measures

Primary Outcomes (1)

• The Ratio of PTS-positive Subjects

  The primary efficacy endpoint will be the proportion of PTS-positive subjects defined as the ratio of PTS-positive subjects to total number of subjects within each study arm/group. Subjects defined as PTS-positive will demonstrate an increase in threshold that is ≥10 dB HL at any frequency from 2-6 kHz post-surgery as compared to baseline audiogram.

  30 days

Secondary Outcomes (1)

• The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift

  30 days

Study Arms (3)

Zonisamide Pre-op + Placebo Post-op

ACTIVE COMPARATOR

For subjects randomized to zonisamide pre-op, the pre-op package will contain one zonisamide capsule (100 mg PO) and the post-op package will contain one placebo capsule that looks, smells, and tastes the same as zonisamide capsules.

Drug: Zonisamide 100Mg Cap; Drug: Placebo

Placebo Pre-op + Placebo Post-op

PLACEBO COMPARATOR

For the subjects randomized to placebo, both pre- and post-op packages will contain placebo capsules that looks, smells, and taste the same as zonisamide capsules.

Drug: Placebo

Placebo Pre-op + Zonisamide Post-op

ACTIVE COMPARATOR

For subjects randomized to zonisamide post-op, the pre-op package will contain one placebo capsule and the post-op package will contain one zonisamide capsule (100 mg PO).

Drug: Zonisamide 100Mg Cap; Drug: Placebo

Interventions

Zonisamide 100Mg Cap DRUG

ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.

Also known as: Zonegran, ZNS

Placebo Pre-op + Zonisamide Post-op; Zonisamide Pre-op + Placebo Post-op

Placebo DRUG

The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.

Also known as: microcrystalline cellulose

Placebo Pre-op + Placebo Post-op; Placebo Pre-op + Zonisamide Post-op; Zonisamide Pre-op + Placebo Post-op

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are scheduled to undergo a skull-based surgery that requires at least 45 minutes of surgical-drilling
• At least 18 years of age
• Air conduction thresholds in the non-operated ears are to be no worse than 25 decibel (dB) hearing loss (HL) for pure tone average 0.5, 1, and 2 kilohertz (kHz) with no individual threshold greater than 30 dB HL, and no worse than 45dB HL at 4 kHz at screening.
• Observed air-bone gap \< 10 dB HL at 0.5, 1, 2, and 4 kHz, with normal tympanometry.
• Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document.

You may not qualify if:

• History of known sulfa allergy or hypersensitivity to carbonic anhydrase inhibitors
• History of moderate-to-severe kidney or liver disease
• Acute viral, bacterial, fungal or parasitic infection
• History of seizures
• Currently pregnant or breast-feeding
• Any current or history of ear disorder and/or central auditory dysfunction in the non-operated ear
• History of ototoxic drug use
• Current use of strong/moderate 3A4 inhibitor/inducer and grapefruit juice

Sponsors & Collaborators

• Washington University School of Medicine: lead
• University of Texas: collaborator
• Gateway Biotechnology, Inc.: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Hearing Loss, Noise-Induced

Interventions

Zonisamide; Capsules; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Hearing Loss, Sensorineural; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Craig Buchman, Lindburg Professor & Chair, Department of Otolaryngology-Head & Neck Surgery
• Organization: Washington University in St. Louis

buchmanc@wustl.edu

314-362-2914

Study Officials

• Craig A Buchman, MD, FACS

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects will be randomized in a balanced fashion into one of 3 arms: Zonisamide 100 mg pre-op, Placebo, or Zonisamide 100 mg post-op. To ensure double-blinding of the trial, each subject will be assigned a previously prepared envelope with one package labeled "1" and designated to be taken 4 hours prior to surgery and another package labeled "2" designated to be taken within 4-12 hours after surgery or when the patient is released clinically to oral medication.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group.

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: February 24, 2021
• Study Start: October 4, 2021
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)