Disappointing results have been reported from a phase 3 study of Keyzilen (Auris Medical Holding AG) in patients with acute inner-ear tinnitus. The study did not meet its two coprimary efficacy endpoints of statistically significant changes in tinnitus loudness and tinnitus burden compared with placebo.
Keyzilen is a small-molecule N-methyl-D-aspartate (NMDA) receptor antagonist formulated in a biocompatible gel for intratympanic injection. Evidence suggests that NMDA receptors in the cochlea play a major role in the occurrence of tinnitus after acute injury to the inner ear, such as from exposure to excessive noise, infections, disturbances in the inner-ear blood supply, or the administration of certain ototoxic drugs. Persistent overexpression of NMDA receptors may lead to pathological excitation of auditory nerve fibers, which the brain perceives as tinnitus. Keyzilen has received a fast track designation from the FDA for the treatment of acute peripheral (inner-ear) tinnitus after traumatic cochlear injury or otitis media in adults.
The randomized, double-blind, placebo-controlled TACTT2 trial was conducted primarily in North America and included 343 patients with acute inner-ear tinnitus after traumatic cochlear injury or otitis media. The patients were randomly assigned to receive either Keyzilen 0.87 mg/mL or placebo. The coprimary endpoints were the improvement in subjective tinnitus loudness from baseline to day 84 and the improvement in tinnitus burden from baseline to day 84, as measured by the Tinnitus Functional Index (TFI).
Treatment with Keyzilen did not demonstrate a statistically significant difference in tinnitus improvement compared with placebo for either endpoint. Keyzilen was well tolerated, with no drug-related serious adverse events. The trial’s primary safety endpoint––the incidence of clinically meaningful hearing deterioration––was low, with no statistically significant difference between the Keyzilen and placebo groups.
Results from a second phase 3 study of Keyzilen (TACTT3) are expected in the fourth quarter of 2016.
TACTT3, which is being conducted in Europe, is a randomized, double-blind, placebo-controlled trial in patients with acute and post-acute inner-ear tinnitus after traumatic cochlear injury or otitis media. The study has enrolled more than 300 patients during the acute tinnitus stage and approximately 330 patients during the post-acute tinnitus stage. The primary endpoint is the change in tinnitus loudness from baseline to day 84. The change in the TFI is the key secondary efficacy outcome.
Source: Auris Medical; August 18, 2016.