Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease.
Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease.
复制标题
DOI：
10.1016/j.trci.2015.04.001
复制
发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Gold M
中科院分区：
文献类型：
--
作者：
Maher-Edwards G;Watson C;Ascher J;Barnett C;Boswell D;Davies J;Fernandez M;Kurz A;Zanetti O;Safirstein B;Schronen JP;Zvartau-Hind M;Gold M
之前对5-羟色胺(5-HT6)受体拮抗剂SB742457的两项研究表明，SB742457可以改善阿尔茨海默病(AD)的认知和整体预后。两项随机、安慰剂对照试验研究了轻中度AD患者的SB742457 15和35 mg(简易精神健康状态检查[MMSE]10-26)。研究1(n=1576)调查了SB742457和多奈哌齐(每天5-10 mg)作为单一治疗6个月的情况。研究2(n=1684)调查了服用多奈哌齐的受试者中的SB742457。24周时的主要终点评估认知(AD评估量表-认知子量表[ADAS-Cog])和全球结果(研究1：基于临床医生访谈的变化印象加上护理者投入[Cibic+]；研究2：临床痴呆症评级-盒子总和[CDR-SB])。对安全性进行了全程评估。这两项研究都未能达到其主要目标的正式统计意义。研究1：SB742457单一疗法与安慰剂在任何终点上都没有统计学意义上的显著差异。多奈哌齐改善了Cibic+，但没有改善ADAS-Cog。研究2：对于ADAS-COG(12、24和48周，但不是36周)、ADCS-ADL(12-36周，但不是48周)和CDR-SB(仅12周)，SB742457 35 mg显示出与安慰剂相比有统计学意义的差异。两项研究都没有达到成功的总体标准，但作为多奈哌齐的辅助药物，与单用多奈哌齐相比，SB742457在认知和ADL方面的持续改善可持续长达48周。临床试验注册：ClinicalTrials.gov：研究1 NCT00708552；研究2 NCT00710684。
Two previous studies of SB742457, a 5-hydroxytryptamine (5-HT6) receptor antagonist, suggested the efficacy of improvements in cognition and global outcome in Alzheimer's disease (AD). Two randomized, placebo-controlled trials investigated SB742457 15 and 35 mg daily in subjects with mild-to-moderate AD (Mini-Mental Health State Examination [MMSE] 10–26). Study 1 (n = 576) investigated SB742457 and donepezil (5–10 mg daily) as monotherapy for 6 months. Study 2 (n = 684) investigated SB742457 in subjects who were maintained on donepezil. Coprimary endpoints at 24 weeks assessed cognition (AD Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global outcome (Study 1: Clinician Interview-Based Impression of Change Plus Caregiver Input [CIBIC+]; Study 2: Clinical Dementia Rating-Sum of Boxes [CDR-SB]). Safety was assessed throughout. Both studies failed to achieve formal statistical significance for their primary objectives. Study 1: SB742457 monotherapy was not statistically significantly different from placebo on any endpoint. Donepezil improved CIBIC+ but not ADAS-Cog. Study 2: SB742457 35 mg showed statistically significant differences relative to placebo for ADAS-cog (weeks 12, 24, and 48, but not week 36), ADCS-ADL (weeks 12–36, but not week 48), and CDR-SB (week 12 only). Neither study met the overall criteria for success, but as an adjunct to donepezil, SB742457 was associated with sustained improvements for up to 48 weeks in cognition and ADL, compared with donepezil alone. Clinical Trial Registration: Clinicaltrials.gov: Study 1 NCT00708552; Study 2 NCT00710684.