title: Selecting appropriate dose regimens for AM-101 in the intratympanic treatment of acute inner ear tinnitus.
abstract: Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small molecule antagonist delivered by intratympanic injection, represents a novel approach to treat acute tinnitus triggered by glutamate excitotoxicity. An earlier double-blind, randomized, placebo-controlled phase II clinical trial (TACTT0) had demonstrated a significant and dose-dependent improvement in tinnitus triggered by acute acoustic trauma or otitis media from baseline to day 90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate dose regimen for this treatment. Outcomes from the TACTT1 trial showed no significant difference in tinnitus improvement between a single-dose treatment and a dose regimen comprising three doses over 2 weeks. Taken together, three injections over 3 consecutive days showed the best results in the two phase II trials, suggesting that repeated and concentrated inhibition of cochlear NMDA receptors provides best treatment effects, while keeping the procedural impact on patients short.
authors: Department of Otolaryngology, Head and Neck Surgery, University of Kansas Medical Center, Kansas City, Kans., USA.
authors: Hinrich
authors: H
authors: Staecker
authors: Kenneth S
authors: KS
authors: Maxwell
authors: John R
authors: JR
authors: Morris
authors: Paul
authors: P
authors: van de Heyning
authors: Krzysztof
authors: K
authors: Morawski
authors: Frank
authors: F
authors: Reintjes
authors: Thomas
authors: T
authors: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069555:Injection, Intratympanic; D008297:Male; D008875:Middle Aged; D014012:Tinnitus / Q000188:drug therapy*; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000187:drug effects; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C000592906:PDCD5 protein, rat