title: Efficacy and safety of AM-101 in the treatment of acute inner ear tinnitus--a double-blind, randomized, placebo-controlled phase II study.
abstract: 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.
  
  
  METHODS
  Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90.
  
  
  METHODS
  Twenty-eight European sites (academic tertiary referral centers and private ENT practices).
  
  
  METHODS
  248 patients aged 16 to 65 years.
  
  
  METHODS
  Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *Department of ENT, Head and Neck Surgery, Antwerp University Hospital, Antwerp, Belgium; †Department of ENT, Head and Neck Surgery, German Armed Forces Hospital Ulm, Ulm, Germany; ‡Department of ENT, Head and Neck Surgery, Virga Jesse Hospital, Hasselt, Belgium; §Medical University of Silesia, Katowice; ∥Dept. of Otolaryngology, Medical University of Warsaw, Warsaw, Poland; and ¶Auris Medical AG, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: van de Heyning
authors.forename: Guido
authors.initials: G
authors.lastname: Muehlmeier
authors.forename: Tony
authors.initials: T
authors.lastname: Cox
authors.forename: Grazyna
authors.initials: G
authors.lastname: Lisowska
authors.forename: Heinz
authors.initials: H
authors.lastname: Maier
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Morawski
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D003627:Data Interpretation, Statistical; D004432:Ear, Middle; D005060:Europe; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007267:Injections; D053583:Interleukin-1beta / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D007759:Labyrinth Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010033:Otitis Media / Q000150:complications; D012405:Round Window, Ear / Q000378:metabolism; D014012:Tinnitus / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D053583:Interleukin-1beta; D007649:Ketamine