Sramek J J, Anand R, Wardle T S, Irwin P, Hartman R D, Cutler N R
California Clinical Trials, Beverly Hills, CA 90211, USA.
Life Sci. 1996;58(15):1201-7. doi: 10.1016/0024-3205(96)00081-1.
SDZ ENA 713 (ENA 713) is an acetylcholinesterase inhibitor being developed as a potential treatment for Alzheimer's disease (AD). A prior Phase II safety and efficacy study used an upper dose limit of 6 mg/day ENA 713. The present study was designed to assess the safety and tolerability of higher doses of ENA 713 in probable AD patients. Fifty AD patients (22M; 28F, mean age 68 yrs, range 45-90) were assigned to a fixed, nine-week dose escalation schedule in which they were randomized to receive up to 12 mg/day of ENA 713 bid (n=20) or tid (n=20), or placebo (n=10) followed by a one-week washout. Mg/day dose escalation for the bid and tid ENA 713 groups was identical, beginning with 2 mg/day on Days 1 to 3 and escalating to 12 mg/day in Weeks 8 and 9. Doses through 12 mg/day were well tolerated. Most adverse events were mild to moderate in severity and of limited duration, most commonly headache, nausea, dizziness, and diarrhea. Three of forty patients on ENA 713 discontinued, all due to adverse events. Two experienced nausea and vomiting; the third experienced an unrelated mild atrial fibrillation.
SDZ ENA 713（ENA 713）是一种乙酰胆碱酯酶抑制剂，正作为治疗阿尔茨海默病（AD）的潜在药物进行研发。之前的一项II期安全性和有效性研究使用的ENA 713剂量上限为6毫克/天。本研究旨在评估更高剂量的ENA 713对可能患有AD的患者的安全性和耐受性。50名AD患者（22名男性；28名女性，平均年龄68岁，年龄范围45 - 90岁）被分配到一个固定的为期九周的剂量递增方案中，他们被随机分为接受每日两次、每次最高12毫克的ENA 713（n = 20）或每日三次（n = 20），或安慰剂（n = 10），随后为期一周的洗脱期。每日两次和每日三次的ENA 713组的毫克/天剂量递增是相同的，从第1至3天的2毫克/天开始，在第8周和第9周递增至12毫克/天。高达12毫克/天的剂量耐受性良好。大多数不良事件的严重程度为轻度至中度，持续时间有限，最常见的是头痛、恶心、头晕和腹泻。40名服用ENA 713的患者中有3人停药，均是由于不良事件。两人出现恶心和呕吐；第三人出现了一次无关的轻度心房颤动。
