{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:01:52Z","timestamp":1790251312841,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the safety and tolerability of repeated intratympanic administration of the gel\u2010formulated NMDA receptor antagonist AM\u2010101\u00a0in acute patients with inner ear tinnitus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Prospective, double\u2010blind, randomized, placebo\u2010controlled study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Sixty\u2010nine secondary and tertiary sites in North America, Europe, and Asia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>In total, 343 subjects with persistent acute tinnitus after traumatic cochlear injury or otitis media were randomized to receive 3\u00a0intratympanic doses of either AM\u2010101 0.87\u00a0mg\/mL or placebo over 3 to 5\u00a0days. They were followed for 84\u00a0days. The primary safety end point was the incidence of a clinically meaningful hearing deterioration from baseline to study day 35. Further safety assessments included tympanic membrane closure rates, analysis of adverse events, hematology, blood chemistry, and vital signs. In addition, data were collected on applied anesthetics and injection techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The treatment was well tolerated, with no intervention\u2010related serious adverse events. The incidence of clinically meaningful hearing deterioration was low, comparable between treatment groups (<jats:italic>P<\/jats:italic> =. 82 for the primary safety end point) and not different between treated and untreated ears in unilaterally treated subjects. The rate of treatment and procedure\u2010related adverse events was similar among treatment groups. The tympanic membrane was closed in 92% of subjects within 1 week and in all subjects by study day 84. Blood values and vital signs were inconspicuous.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Repeated intratympanic injections of AM\u2010101 over a 3\u2010 to 5\u2010day period appear to be safe and well tolerated, demonstrating the ability to potentially use this delivery approach over longer time periods.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599817711378","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T11:12:27Z","timestamp":1497352347000},"page":"478-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Safety of Repeated\u2010Dose Intratympanic Injections with AM\u2010101\u00a0in Acute Inner Ear Tinnitus"],"prefix":"10.1002","volume":"157","author":[{"given":"Hinrich","family":"Staecker","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of Kansas Medical Center Kansas City Kansas 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