目的:确定鼓室内OTO-104治疗梅尼埃病的疗效。
方法:三个随机,双盲,安慰剂对照,OTO-104在梅尼埃病患者中的多中心研究。
方法:美国和整个欧洲。
方法:患有梅尼埃病的患者,年龄18~85岁。
方法:所有三项研究都是根据类似的方案进行的,在1个月的导入期后,符合条件的患者接受了单次鼓室内注射12mgOTO-104(地塞米松在热敏泊洛沙姆中的耳制剂)或安慰剂(1:1),并观察了3个月.
方法:主要疗效终点是通过第3个月的确定性眩晕天数(DVD)来测量的。次要目标是OTO-104安全性和耐受性,包括不良事件,测听法,鼓室测压,和耳镜检查。
结果:尽管在所有三项研究中,与安慰剂相比,OTO-104在DVD中的减少幅度更大,与安慰剂(主要疗效终点)相比,仅在一项研究中达到统计学意义,AVERTS-2研究(n=174,p=0.029)。在该研究中,继发性眩晕疗效终点在第3个月时具有统计学意义,包括眩晕严重程度,眩晕对日常活动(在家生病或卧床不起的日子)的影响,和眩晕频率。在AVERTS-1研究中,不符合主要终点,对之前未接受过鼓室内类固醇注射的115例患者(占研究人群的69.7%)进行的亚组分析显示,OTO-104患者在第3个月时的平均DVD显著低于接受安慰剂的患者(OTO-104为1.9,安慰剂为3.0;p=0.045).重要的是,在梅尼埃疾病患者的研究中观察到显著的安慰剂反应.OTO-104和鼓室内注射程序耐受性良好。
结论:在所有三个高质量中,随机化,双盲,安慰剂对照,多中心研究,在Ménière病患者中,单次鼓室内注射12mgOTO-104与安慰剂相比,眩晕的减少幅度更大,但是仅在一项研究中证明了与安慰剂的统计学分离。OTO-104安全且耐受性良好。(Otonomy,公司资助;NCT02717442、NCT02612337、NCT03664674)。
To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière\'s disease.
Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière\'s disease.
The United States and throughout Europe.
Individuals with Ménière\'s disease aged 18 to 85 years.
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.
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.
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.
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).