Efficacy of SPI-1005 for Prevention of Noise-Induced Hearing Loss: Phase 2 Clinical Trial Results

Abstract

Objectives:

Determine the safety and efficacy of SPI-1005, a novel oral glutathione peroxidase (GPx) mimic and inducer, in preventing and treating noise-induced hearing loss (NIHL) in adults ranging from slight hearing loss (≤25 dBHL) to normal hearing.

Methods:

Randomized double blind placebo controlled Phase 2 clinical trial conducted December 2012 through November 2013. A total of 83 subjects at the University of Florida were enrolled and treated with either placebo or SPI-1005 prior to a single iPod sound exposure lasting 4 hours that induced a slight temporary threshold shift (TTS). The incidence (≥10 dBHL), severity (dBHL), and duration (up to 1 week post sound) of the TTS were determined by serial pure tone audiometry. The intervention (200, 400, or 600 mg SPI-1005 twice daily × 4 days) was compared with matching placebo in reducing the TTS. Significance was determined by 2-tailed t tests comparing a specific SPI-1005 treatment group versus placebo.

Results:

Oral SPI-1005 treatment showed a significant reduction in TTS incidence (60% vs 20%, P < .01), severity (4.2 vs 1.1 dBHL at 4 kHz, P < .01), and duration (24 vs 1.3 hours, P < .01). SPI-1005 treatment was well tolerated with no drug-related adverse events (CBC, Chem20, chest x-ray).

Conclusions:

SPI-1005 treatment demonstrated clinically relevant reductions in TTS induced by loud sound exposure. Multiday treatment with all SPI-1005 dosages was well tolerated. These data support the continued development of SPI-1005 in noise exposed populations and the GPx mechanism of action in preventing and treating NIHL.