Noise-Induced Hearing Loss-Acute Exposure Treatment

Phase 2

Terminated

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.

Detailed Description: This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group. After being informed about the study expectations and potential risks, all individuals providing written informed consent will undergo screening to determine eligibility for study entry.

Participants who meet the eligibility requirements will be randomized in a balanced fashion into one of 3 arms:

Group 1) Zonisamide 100 milligrams (mg) pre-op + Placebo post-op; Group 2) Placebo pre- + placebo post-op; and Group 3) Zonisamide 100 mg post-op + placebo post-op

Recruitment & Eligibility

Inclusion Criteria

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.

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Zonisamide Pre-op + Placebo Post-op	Zonisamide 100Mg Cap	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.
Zonisamide Pre-op + Placebo Post-op	Placebo	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.
Placebo Pre-op + Placebo Post-op	Placebo	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.
Placebo Pre-op + Zonisamide Post-op	Zonisamide 100Mg Cap	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).
Placebo Pre-op + Zonisamide Post-op	Placebo	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).

Primary Outcome Measures

Name	Time	Method
The Ratio of PTS-positive Subjects	30 days	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.

Secondary Outcome Measures

Name	Time	Method
The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift	30 days	The secondary efficacy outcome measures will be the rate of temporary cochlear change as measured by a DPOAE amplitude shift at any frequency that is significantly greater than the stability of each measurement (i.e., 95% confidence interval of each measurement do not overlap). The rate of DPOAE shift is the ratio of DPOAE shift-positive subjects to total subjects within each arm.