The AudioNotch Tinnitus Treatment Blog

One of the challenging things for patients who acutely develop tinnitus is the absence of therapeutic interventions available in the acute phase (i.e. shortly after a person develops tinnitus in a rapid fashion). Current theory surrounding the pathophysiology of tinnitus is that there is a “therapeutic window” in the acute term where the brain’s plasticity is still open to modification. Experiments have been done with N-acetylcysteine, for example, which was given to troops preventively in order to offset the excitotoxicity that causes hair cell death in the cochlea following acoustic trauma. However, after the acute phase, the brain seems to “make permanent” the changes that cause the tinnitus percept – so intervention in the therapeutic window is a good therapeutic target. A new drug, AM-101, continues to progress in clinical trials. How does it work?

AM-101 is a small molecule N-methyl-D-aspartate (NMDA) receptor antagonist formulated in a biocompatible gel for intratympanic injection. 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. Cochlear excitotoxicity may be triggered by, for example, trauma (e.g. exposure to excessive noise), neuroinflammation, disturbances in inner ear blood supply (anoxia/ischemia), or the administration of certain ototoxic drugs. It has been proposed that the upregulation of NMDA receptors induced by cochlear excitotoxicity is responsible for aberrant excitation of auditory nerve fibers, which is perceived as tinnitus.

The drug will be tested in Europe and North America:

Auris Medical today announced enrollment of the first patient into in the TACTT3¹ clinical trial – a phase 3 study designed to evaluate the efficacy, safety and tolerability of intratympanic injections of AM-101 in the treatment of acute peripheral tinnitus following traumatic cochlear injury or otitis media. The TACTT3 study will enroll 600 patients at more than 60 European sites: 300 during the acute tinnitus stage (up to 3 months from onset) and 300 during the post-acute tinnitus stage (4 to 12 months from onset).

It is one of two pivotal double-blind, placebo-controlled trials in Auris Medical’s phase 3 development program with AM-101. The second study, TACTT2, is expected to start enrollment in the United States and Canada shortly. All participants completing one of the TACTT studies and continuing to meet certain criteria will be eligible to enter an open label safety study (AMPACT1, respectively AMPACT2)² and receive up to 3 treatment cycles with AM-101 over up to 9 months.

This won’t help people with chronic tinnitus but it may help prevent acute tinnitus from becoming a chronic, permanent condition.