Efficacy and safety of AM-101 in the treatment of acute inner ear tinnitus--a double-blind, randomized, placebo-controlled phase II study.

OBJECTIVE: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. STUDY DESIGN:Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90. SETTING:Twenty-eight European sites (academic tertiary referral centers and private ENT practices). PATIENTS:248 patients aged 16 to 65 years. INTERVENTIONS: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. RESULTS: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. CONCLUSION: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.