Trial Outcomes & Findings for Noise-Induced Hearing Loss-Acute Exposure Treatment (NCT NCT04768569)

Last Updated: 2025-01-15

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

30 days

Results posted on

2025-01-15

Participant Flow

24 participants were consented for the study and enrolled. However, after consent but before any study activities could occur (including randomization), one participant chose to no longer participate. This excluded participant did not complete any study activities after consent. Thus, only 23 participants were consented and completed study activities including randomization.

Participant milestones

Participant milestones
Measure	Zonisamide Pre-op + Placebo Post-op 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 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Placebo Post-op 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Zonisamide Post-op 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). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
Overall Study STARTED	8	7	8
Overall Study COMPLETED	8	7	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Noise-Induced Hearing Loss-Acute Exposure Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide Pre-op + Placebo Post-op n=8 Participants 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 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Placebo Post-op n=7 Participants 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Zonisamide Post-op n=8 Participants 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). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Total n=23 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 15.2 • n=5 Participants	49.7 years STANDARD_DEVIATION 12.37 • n=7 Participants	53.6 years STANDARD_DEVIATION 9.75 • n=5 Participants	51.0 years STANDARD_DEVIATION 12.23 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	8 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: 30 days

Population: ITT Sample Set

Outcome measures

Outcome measures
Measure	Zonisamide Pre-op + Placebo Post-op n=8 Participants 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 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Placebo Post-op n=7 Participants 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Zonisamide Post-op n=8 Participants 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). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
The Ratio of PTS-positive Subjects PTS-positive Subjects at Post-op 30 Days Visit	3 Participants	1 Participants	1 Participants
The Ratio of PTS-positive Subjects PTS-negative Subjects at Post-op 30 Days Visit	5 Participants	6 Participants	7 Participants

SECONDARY outcome

Timeframe: 30 days

Population: ITT Sample

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.

Outcome measures

Outcome measures
Measure	Zonisamide Pre-op + Placebo Post-op n=8 Participants 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 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Placebo Post-op n=7 Participants 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Zonisamide Post-op n=8 Participants 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). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift No shift	2 Participants	2 Participants	1 Participants
The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift Shift	4 Participants	4 Participants	1 Participants
The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift Excluded	2 Participants	1 Participants	6 Participants

Adverse Events

Zonisamide Pre-op + Placebo Post-op

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo Pre-op + Placebo Post-op

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo Pre-op + Zonisamide Post-op

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zonisamide Pre-op + Placebo Post-op n=8 participants at risk 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 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Placebo Post-op n=7 participants at risk 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.	Placebo Pre-op + Zonisamide Post-op n=8 participants at risk 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). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
Injury, poisoning and procedural complications Toxicity to Various Agents	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/7 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Nervous system disorders Brain Oedema	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/7 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Nervous system disorders Ischaemic stroke	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/7 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Nervous system disorders Aphasia	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/7 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Nervous system disorders Encephalopathy	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/7 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	12.5% 1/8 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Gastrointestinal disorders Dysphagia	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	14.3% 1/7 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.
Nervous system disorders Cerebrial Infarction	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	14.3% 1/7 • Number of events 1 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.	0.00% 0/8 • Adverse Events were assessed from time of oral dose at the surgery visit to the final visit (30 days post-op, +/- 3 days). Total period of time over which adverse event data were collected were 30 days +/- 3 days.

Other adverse events

Additional Information

Dr. Craig Buchman, Lindburg Professor & Chair, Department of Otolaryngology-Head & Neck Surgery

Washington University in St. Louis

Phone: 314-362-2914

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place