Efficacy and Safety of AM-101 in the Treatment of Acute Inner Ear Tinnitus—A Double-Blind, Randomized, Placebo-Controlled Phase II Study

Abstract

ObjectiveTo 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 DesignProspective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90.SettingTwenty-eight European sites (academic tertiary referral centers and private ENT practices).Patients248 patients aged 16 to 65 years.InterventionsThree intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days.Main Outcome MeasuresEfficacy 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.ResultsThe 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.ConclusionThe 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.

Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus

“…In focusing on traumatic origins and the acute stage as well as targeted delivery of the compound to the cochlea, AM-101 has been evaluated under relatively well defined conditions. The results reported here and in phase II clinical trials [29] show that NMDA receptor antagonists have the potential of being used for local/cochlear treatment of tinnitus in patients.…”

“…It is delivered locally in the form of a hyaluronic acid gel applied to the round window membrane. This approach was previously tested in two clinical studies [28,29] and provides for a highly targeted cochlear therapy with only minimal systemic exposure [30,31]. This method has proven to be effective in patients suffering from acute tinnitus triggered by noise trauma or otitis media [29].…”

Effect of a 4-Week Treatment with Cilostazol in Patients with Chronic Tinnitus: A Randomized, Prospective, Placebo-controlled, Double-blind, Pilot Study

“…Unfortunately, the correction was thought to be insufficient due to the small number of study patients, making the analysis of the THI scores hard to interpret. The efficacy of medication for tinnitus can be measured audiologically through tinnitus loudness matching [27,28] . In our present study, however, tinnitus characteristics of pitch and loudness did not show any significant within-and between-group improvements after medication.…”

Intratympanale Injektionstherapie bei therapierefraktärem Hörsturz

“…Insgesamt sind auch in der Literatur nur sehr wenige Auffällig-keiten beschrieben [17,40,33,37,46]. Zu den häufigsten Problemen wurden Defekte des Trommelfells angegeben, die insbesondere dann auftraten, wenn eine Parazentese, ggf.…”