Title: Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial
Kil, J et al.
What You Need to Know:
According to results of a phase 2 trial, ebselen, a glutathione peroxidase 1 mimic, was found to be safe as well effective for the prevention of noise-induced hearing loss when dosed at 400mg twice daily.
- Double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of ebselen in preventing noise-induced hearing loss in healthy adult patients 18-31 years old
- 83 patients were randomized (1:1:1:1) to receive 200mg (n=22), 400mg (n=20), or 600mg (n=21) of ebselen administered orally or placebo (n=20)
- Study medication was administered twice daily for 4 days and was initiated 2 days before completing a calibrated sound challenge (4 hours of music delivered via earphones)
- Primary endpoint: “mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant”
- Efficacy analysis included all patients who received the sound challenge as well as ≥1 dose of study medication; safety analysis included all patients
- 2 patients from the 200mg group did not meet inclusion criteria, and were therefore excluded from the study
- Mean TTS at 4 kHz for patients receiving 400mg of ebselen compared to placebo: 1.32 dB (SE: 0.91) vs 4.07 dB (SE: 0.90), respectively (reduction of 68%; difference: -2.75 dB; 95% CI: -4.54, -0.97; P=0.0025)
- Mean TTS at 4 kHz for patients receiving 200mg of ebselen compared to placebo: 3.23 dB (SE: 0.91) vs 4.07 dB (SE: 0.90), respectively (reduction of 21%; difference: −0.84 dB; 95% CI: −2.63, 0.94; p=0.3542)
- Mean TTS at 4 kHz for patients receiving 600mg ebselen compared to placebo: 3.81 dB (SE: 0.90) vs 4.07 dB (SE: 0.90), respectively (reduction of 7%; difference: −0.27 dB; 95% CI: −2.03, 1.50; p=0.7659)
- Safety: all doses of ebselen were well tolerated and “no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group”