Supplementary Material for: A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

<b><i>Aim:</i></b> To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm² and titrated to 10 cm² after 4 weeks) is well tolerated in Japanese patients with Alzheimer's disease (AD) as compared to 3-step titration (initiated at 2.5 cm² and titrated by 2.5 cm² every 4 weeks to 10 cm²). <b><i>Methods:</i></b> A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. <b><i>Results:</i></b> Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108) were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6), falling within the prespecified acceptance range. <b><i>Conclusion:</i></b> The tolerability of two different titration schemes was similar in Japanese patients with AD.

<b><i>研究目的：</i></b> 旨在探讨相较于三步剂量滴定法（初始剂量为2.5 cm²，每4周递增2.5 cm²直至10 cm²），采用一步剂量滴定法（初始剂量为5 cm²，4周后递增至10 cm²）的卡巴拉汀透皮贴剂（rivastigmine patch）在日本阿尔茨海默病（Alzheimer's disease, AD）患者中的耐受性表现。<b><i>研究方法：</i></b> 本研究于2012年7月至2014年5月在日本开展，为一项为期24周的多中心随机双盲临床试验。将年龄50~85岁的轻中度阿尔茨海默病患者按1:1比例随机分配至一步滴定组或三步滴定组，接受每日一次的卡巴拉汀透皮贴剂治疗。本研究的主要终点为因不良事件停药的患者比例。<b><i>研究结果：</i></b> 共计216例患者完成随机入组，其中215例（一步组n=107；三步组n=108）纳入安全性分析。主要终点结果显示，一步组与三步组的因不良事件停药率分别为15.0%与18.5%。观察到的组间治疗差异为-3.6%（95%置信区间：-17.0，9.6），处于预先设定的可接受范围内。<b><i>研究结论：</i></b> 两种剂量滴定方案在日本阿尔茨海默病患者中的耐受性相当。