Dataset Information

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

ABSTRACT:

Objective

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).

SUBMITTER: Phillips J

PROVIDER: S-EPMC10289225 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Phillips John J Mikulec Anthony A AA Robinson James M JM Skarinsky David D Anderson Jeffery J JJ

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 20230422 6

<h4>Objective</h4>To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease.<h4>Study designs</h4>Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease.<h4>Setting</h4>The United States and throughout Europe.<h4>Patients</h4>Individuals with Ménière's disease aged 18 to 85 years.<h4>Interventions</h4>All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in peri ...[more]

PMID: 37185596

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