title: A randomized, double-blind, placebo-controlled clinical study to assess safety and clinical activity of OTO-104 given as a single intratympanic injection in patients with unilateral Ménière's disease.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and clinical activity of a single intratympanic injection of OTO-104, sustained-release dexamethasone formulation, in patients with unilateral Ménière's disease.
  
  
  METHODS
  Prospective, double-blind, randomized, placebo-controlled, dose-escalation study of 16 weeks' (4-wk lead-in before dosing; 12-wk follow-up after dosing) duration for each patient.
  
  
  METHODS
  Fifteen centers (physician offices and academic or tertiary referral centers).
  
  
  METHODS
  Forty-four patients aged 22 to 75 years.
  
  
  METHODS
  Single intratympanic injection of OTO-104 (3 or 12 mg) or placebo.
  
  
  METHODS
  Safety and tolerability were assessed via adverse event reports, otoscopy, audiometry, and tympanometry. Clinical activity was assessed primarily as changes in vertigo frequency.
  
  
  RESULTS
  OTO-104 was well tolerated, with no impact on hearing function. Plasma levels were observed in a few patients and were barely quantifiable. The most frequently reported adverse event considered related to investigational product was tympanic membrane perforation; no clinical sequelae were associated with these perforations and all were graded mild or moderate. At Month 3, the observed mean ± standard deviation (SD) change from baseline in vertigo frequency was -0.124 ± 0.153, -0.147 ± 0.166, and -0.211 ± 0.153 for the placebo, 3-mg OTO-104, and 12-mg OTO-104 groups, respectively; corresponding to 42%, 56% and 73% reductions in vertigo frequency, respectively. Similar results were observed for tinnitus, measured by the Tinnitus Handicap Inventory (THI-25).
  
  
  CONCLUSIONS
  OTO-104 was safe and well tolerated. Although the sample size was small, the data suggest 12 mg of OTO-104 was associated with a clinically meaningful reduction in vertigo frequency compared to placebo 3 months after treatment.
authors.affiliation: Medical University of South Carolina, Department of Otolaryngology, Charleston, South Carolina, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lambert
authors.forename: Shaun
authors.initials: S
authors.lastname: Nguyen
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Maxwell
authors.forename: Debara L
authors.initials: DL
authors.lastname: Tucci
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Lustig
authors.forename: Malcolm
authors.initials: M
authors.lastname: Fletcher
authors.forename: Moraye
authors.initials: M
authors.lastname: Bear
authors.forename: Carl
authors.initials: C
authors.lastname: Lebel
mesh_terms: D000328:Adult; D000368:Aged; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000188:drug therapy*; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D014432:Tympanic Membrane; D014717:Vertigo / Q000188:drug therapy*
chemical_list: D005938:Glucocorticoids; D010919:Placebos; D003907:Dexamethasone