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Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies

To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease. STUDY DESIGNS: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease. SETTING: The United States and throughout Europe. PATIENTS: Indiv...

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Autores principales: Phillips, John, Mikulec, Anthony A., Robinson, James M., Skarinsky, David, Anderson, Jeffery J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289225/
https://www.ncbi.nlm.nih.gov/pubmed/37185596
http://dx.doi.org/10.1097/MAO.0000000000003886
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author Phillips, John
Mikulec, Anthony A.
Robinson, James M.
Skarinsky, David
Anderson, Jeffery J.
author_facet Phillips, John
Mikulec, Anthony A.
Robinson, James M.
Skarinsky, David
Anderson, Jeffery J.
author_sort Phillips, John
collection PubMed
description To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease. STUDY DESIGNS: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease. SETTING: The United States and throughout Europe. PATIENTS: Individuals with Ménière's disease aged 18 to 85 years. INTERVENTIONS: All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months. MAIN OUTCOME MEASURES: The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations. RESULTS: Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated. CONCLUSIONS: In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated. (Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674).
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spelling pubmed-102892252023-06-24 Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies Phillips, John Mikulec, Anthony A. Robinson, James M. Skarinsky, David Anderson, Jeffery J. Otol Neurotol Vestibular Disorders To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease. STUDY DESIGNS: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease. SETTING: The United States and throughout Europe. PATIENTS: Individuals with Ménière's disease aged 18 to 85 years. INTERVENTIONS: All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months. MAIN OUTCOME MEASURES: The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations. RESULTS: Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated. CONCLUSIONS: In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated. (Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674). Lippincott Williams & Wilkins 2023-07 2023-04-22 /pmc/articles/PMC10289225/ /pubmed/37185596 http://dx.doi.org/10.1097/MAO.0000000000003886 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Vestibular Disorders
Phillips, John
Mikulec, Anthony A.
Robinson, James M.
Skarinsky, David
Anderson, Jeffery J.
Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title_full Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title_fullStr Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title_full_unstemmed Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title_short Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies
title_sort efficacy of intratympanic oto-104 for the treatment of ménière's disease: the outcome of three randomized, double-blind, placebo-controlled studies
topic Vestibular Disorders
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289225/
https://www.ncbi.nlm.nih.gov/pubmed/37185596
http://dx.doi.org/10.1097/MAO.0000000000003886
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