Key results from Auris Medical’s phase IIb study with AM-101, a novel intratympanic (IT) treatment for acute inner ear tinnitus, were presented at the recent 6th International TRI Tinnitus Conference in Bruges, Belgium. The study demonstrated that the treatment was well tolerated and safe and showed a statistically significant reduction in various tinnitus measures as compared to placebo.

AM-101 contains a small molecule that selectively blocks N-methyl-D-aspartate (NMDA) receptors. Emerging evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus following inner ear excitotoxicity, which is characterized by excessive synaptic release of glutamate, the principal neurotransmitter in the auditory system. It has been hypothesized that the upregulation of NMDA receptors induced by cochlear excitotoxicity is responsible for aberrant excitation of auditory nerve fibers, which is perceived as tinnitus.

Auris Medical’s double-blind, randomized, placebo-controlled, parallel-dose phase IIb study with AM-101 was conducted in Germany, Belgium, Poland, and the Netherlands, involving almost 30 sites. A total of 248 patients suffering from persistent acute inner ear tinnitus were randomized to receive 3 IT injections of either AM-101 at 0.27 or 0.81 mg/ml or placebo over 3 consecutive days. Participants’ tinnitus had to be triggered by acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or otitis media after a recent inciting incident. Study participants were monitored over 90 days.

In terms of safety and local tolerance, AM-101 showed no drug-related impact on hearing function. As for efficacy, the study demonstrated a dose-dependent improvement in various measures of the tinnitus symptom and its impact.

Most notably, patients suffering from acute tinnitus with established cochlear origin, such as noise trauma or otitis media, who received AM-101 at 0.81 mg/ml showed a statistically significant improvement (p <0.05 or <0.01) in tinnitus loudness, annoyance, as well as tinnitus-related sleep difficulties and activity and participation limitations. The researchers measured results using a standard tinnitus impairment questionnaire known as "TBF-12," which was given to patients before and after treatment or sham treatment.  

In most cases, the treatment effect started to appear within a few days from administration and continued to increase over the follow-up period. After 90 days, average reductions from baseline levels exceeded 50% for subjective loudness, annoyance, and sleep difficulties, and close to 50% for the TBF-12 score. Effects were somewhat less pronounced in patients with bilateral rather than unilateral tinnitus since only one ear was treated in the study as a precautionary safety measure.

However, efficacy outcomes with patients suffering from tinnitus related to ISSNHL were not conclusive for that subgroup overall, owing to an unexpectedly large rate of spontaneous recovery.

Based on the positive outcomes from the phase IIb study, Auris Medical is moving ahead with the clinical development of AM-101, and is currently in discussion with regulatory agencies on the design for the planned phase III studies.

More detailed information on the phase IIb clinical trial will be published in a scientific journal, although the press release didn’t state any publication or time frame.

SOURCE: Auris Medical