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.

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 Meniere's disease. STUDY DESIGN: 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. SETTING: Fifteen centers (physician offices and academic or tertiary referral centers). PATIENTS: Forty-four patients aged 22 to 75 years. INTERVENTION: Single intratympanic injection of OTO-104 (3 or 12 mg) or placebo. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.