Dataset from A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.

Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG. This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with the currently approved AD medication, Aricept (donepezil). RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects their response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.

罗格列酮（Rosiglitazone，RSG）已通过临床研究验证，并获美国食品药品监督管理局（FDA）批准用于治疗2型糖尿病（type II diabetes mellitus）——该病的发病机制为机体无法有效利用葡萄糖。本研究使用的试验药物RSG XR为罗格列酮的缓释剂型。本研究旨在评估RSG XR与当前获批的阿尔茨海默病（Alzheimer's disease，AD）治疗药物多奈哌齐（Aricept，donepezil）联合使用时，能否安全为轻中度阿尔茨海默病患者带来临床获益。RSG XR是阿尔茨海默病治疗的全新思路，本研究同时将通过考察受试者的遗传构成对试验药物应答的影响，探索阿尔茨海默病治疗的新路径。此前已有临床数据显示罗格列酮可能对阿尔茨海默病患者有益，相关证据最初来自华盛顿大学开展的一项小型研究，其后又有葛兰素史克（GSK）在欧洲与新西兰开展的更大规模研究。在第一项研究中，每日一次服用罗格列酮、持续6个月的受试者，在三项记忆与认知能力测试中的得分显著高于未服用罗格列酮的受试者。在葛兰素史克的研究中，似乎从罗格列酮XR治疗中获益最多的人群具有特定的遗传模式：他们不携带会表达载脂蛋白Eε4（apolipoprotein E ε4，APOE ε4）的基因。携带APOE ε4基因的受试者可能有两份该基因（分别来自父母双方），或仅携带一份APOE ε4基因，即从父母一方继承的是APOE ε2或APOE ε3亚型基因，而非APOE ε4。携带一份APOE ε4基因的受试者认知能力维持原有水平，而携带两份APOE ε4基因的受试者在6个月治疗期间认知能力持续下降。本研究将针对携带或不携带APOE ε4基因的人群，更直接地评估RSG XR的疗效。