背景:Deutrabenazine是一种囊泡单胺转运蛋白2抑制剂,用于治疗迟发性运动障碍(TD)和与亨廷顿病(HD)相关的舞蹈病。为了加强对各个试验中安全信号的检测,在TD和HD舞蹈病中进行了盐酸丁苯那嗪的综合安全性分析。
方法:对于TD,纳入了两项为期12周的关键研究(ARM-TD和AIM-TD)和开放标签扩展(OLE)研究(RIM-TD)第15周的安全性数据.数据通过德丁苯那嗪治疗组和安慰剂进行分析。对于HD,我们对之前接受过安慰剂的患者进行了为期12周的关键性研究(First-HD)和OLE研究(ARC-HD)至第15周的安全性数据进行了整合.从关键研究中比较了对丁苯那嗪的综合数据与安慰剂。
结果:对于TD,与安慰剂组(n=130)相比,deutrabenazine(n=384)的耐受性普遍良好.不良事件(AE)发生率在反应驱动的deutrabenazine与固定剂量的deutrabenazine和安慰剂组相比,在数值上较高。分别(任何AE,59.5%vs44.4-50.0%和53.8%;治疗相关不良事件,38.1%比18.1-25.0%和30.8%)。在deutrabenazine组中,有2.8-8.3%的患者报告了严重的AE,在安慰剂组中为6.9%。常见的不良事件(≥4%)包括头痛,嗜睡,恶心,焦虑,疲劳,口干,和腹泻。滴定期间AE发生率高于维持期间。对于HD,与安慰剂(n=45;任何AE,64.3%vs60.0%;治疗相关不良事件,38.1%vs26.7%);对于deutrabenazine和安慰剂组,报告的严重不良事件比例相似,2.4%和2.2%,分别。常见的不良事件(≥4%)包括易怒,fall,抑郁症,口干,和疲劳。
结论:来自TD研究的综合分析和HD舞蹈病研究的综合分析的数据表明,对丁苯那嗪具有良好的安全性,并且在适应症中具有良好的耐受性。
背景:ClinicalTrials.gov标识符,NCT02291861,NCT02195700,NCT01795859,NCT02198794,NCT01897896。
意外运动通常是亨廷顿病的第一个征兆。这种类型的意外运动在亨廷顿病中被称为舞蹈症。迟发性运动障碍会导致意外的身体运动。Deutrabenazine是一种用于治疗两种运动的药物。本报告总结了五项临床研究中对丁苯那嗪的安全性。通过不良事件(副作用)评估安全性。比较了对丁苯那嗪和非活性治疗(安慰剂)之间的不良事件。还比较了严重的不良事件。严重不良事件导致实质性损害或中断。在亨廷顿病研究的迟发性运动障碍和舞蹈病中,大多数患者继续服用盐酸丁苯那嗪。不良事件不是停止治疗的常见原因。对于迟发性运动障碍,对丁苯那嗪(≤60%)和安慰剂(54%)的不良事件发生率相似.严重不良事件的发生率也相似,对于deutrabenazine(≤8%)和安慰剂(7%)。不良事件倾向于在治疗早期报告。常见的不良事件是头痛,困倦,恶心,焦虑,疲劳,口干,和腹泻。对于亨廷顿病的舞蹈病,deutrabenazine(64%)和安慰剂(60%)的不良事件发生率相似.严重不良事件的发生率也相似,对于deutrabenazine(2%)和安慰剂(2%)。易怒,fall,抑郁症,口干,疲劳是常见的不良事件。在两种情况下,deutrabenazine和安慰剂之间的不良事件相似。对于亨廷顿病患者的迟发性运动障碍或舞蹈病患者,Deutrabenazine具有良好的耐受性。
BACKGROUND: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted.
METHODS: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study.
RESULTS: For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4-50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1-25.0% and 30.8%). Serious AEs were reported for 2.8-8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue.
CONCLUSIONS: Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications.
BACKGROUND: ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896.
Unintended movements are often the first sign of Huntington disease. This type of unintended movement is called chorea in Huntington disease. Tardive dyskinesia causes unintended body movements. Deutetrabenazine is a medicine used to treat both types of movements. This report summarizes deutetrabenazine safety across five clinical studies. Safety was assessed via adverse events (side effects). Adverse events were compared between deutetrabenazine and inactive treatment (placebo). Serious adverse events were also compared. Serious adverse events cause substantial impairment or disruption. In tardive dyskinesia and chorea in Huntington disease studies, most patients kept taking deutetrabenazine. Adverse events were not a common reason to stop treatment. For tardive dyskinesia, adverse event rates were similar between deutetrabenazine (≤ 60%) and placebo (54%). Serious adverse event rates were also similar for deutetrabenazine (≤ 8%) and placebo (7%). Adverse events tended to be reported earlier in treatment. Common adverse events were headache, sleepiness, nausea, anxiety, fatigue, dry mouth, and diarrhea. For chorea in Huntington disease, adverse event rates were similar for deutetrabenazine (64%) and placebo (60%). Serious adverse event rates were also similar for deutetrabenazine (2%) and placebo (2%). Irritability, fall, depression, dry mouth, and fatigue were common adverse events. Adverse events were similar between deutetrabenazine and placebo in both conditions. Deutetrabenazine was well tolerated for patients with either tardive dyskinesia or chorea in Huntington disease.