AM-101 Tinnitus Results
Some of you may be aware of a new drug in development for the treatment of acute tinnitus acquired due to noise trauma. Noise trauma actually kills inner ear hair cells not via direct physical trauma, but via excitotoxicity from an increase in glutamate neurotransmitters. The AM-101 drug is designed to specifically counteract this process. Results of experiments thus far have provoked qualified interest. I’m paraphrasing here, but the idea seems to be preventing the “centralization” of the recurrent neural feedback loops that are theorized to result in chronic tinnitus by restoring the peripheral input to the ear and preventing the cutting off of auditory input that triggers the development of tinnitus.
To evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media.
Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90.
Twenty-eight European sites (academic tertiary referral centers and private ENT practices).
248 patients aged 16 to 65 years.
Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days.
Main Outcome Measures
Efficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events.
The study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated.
The study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests.