Wolfe S G, Chey W Y, Washington M K, Harding J, Heath A T, McSorley D J, Dukes G E, Hunt C M
Gastroenterology Clinical Development, Glaxo Wellcome, Research Triangle Park, North Carolina, USA.
Am J Gastroenterol. 2001 Mar;96(3):803-11. doi: 10.1111/j.1572-0241.2001.03626.x.
Alosetron (Lotronex) is a new therapeutic agent for irritable bowel syndrome (IBS) in women with diarrhea-predominant IBS. This multicenter randomized, double-blind, placebo-controlled study assessed the safety and tolerability of alosetron during long-term (< or = 12 months) treatment.
A total of 859 subjects (637 female and 222 male) with IBS were enrolled from 130 sites in the United States and were randomized 3:1 to receive 1 mg alosetron or placebo b.i.d. for 48 wk; of the subjects, 649 (76%) were randomized to the alosetron group and 212 (24%) to the placebo group. Of the original group, 850 subjects received at least one dose of alosetron (n = 640) or placebo (n = 210).
In all, 59% of the subjects completed the study. Safety data were similar in treatment groups and within age, sex, racial origin, and hormone use. Adverse events were reported by 83% (530/640) and 76% (159/210) of subjects in the alosetron and placebo groups, respectively, (p < 0.05) and were similar with the exception of constipation; 32% of subjects receiving alosetron reported constipation, compared to 5% in the placebo group (p < 0.001). Most reports (72%) of constipation were of mild or moderate severity, and 66% of subjects with constipation had single episode of 8 days median duration. Constipation occurred a median of 13 days after initiating treatment and resolved spontaneously, with laxative, or after a brief interruption of therapy. Of the subjects, 4% (11/210) in the alosetron and 5% (28/ 640) in the placebo group experienced serious adverse events. Two deaths occurred in subjects with pre-existing cardiovascular risk factors; neither death was attributed to the study drug.
Alosetron 1 mg b.i.d. for 12 months was well tolerated. Constipation is the most frequent adverse event, with a higher incidence of transient constipation in alosetron-treated patients, typically occurring in the first month of treatment.
阿洛司琼（洛哌丁胺）是一种用于治疗以腹泻为主型肠易激综合征（IBS）女性患者的新型治疗药物。这项多中心随机、双盲、安慰剂对照研究评估了阿洛司琼长期（≤12个月）治疗期间的安全性和耐受性。
共有859名IBS患者（637名女性和222名男性）从美国130个研究点入组，按3:1随机分组，接受1毫克阿洛司琼或安慰剂，每日两次，共48周；其中，649名（76%）患者被随机分入阿洛司琼组，212名（24%）患者被分入安慰剂组。在最初的研究组中，850名患者接受了至少一剂阿洛司琼（n = 640）或安慰剂（n = 210）。
总体而言，59%的患者完成了研究。治疗组之间以及在年龄、性别、种族和激素使用情况方面的安全性数据相似。阿洛司琼组和安慰剂组分别有83%（530/640）和76%（159/210）的患者报告了不良事件（p < 0.05），除便秘外其他不良事件相似；接受阿洛司琼治疗的患者中有32%报告便秘，而安慰剂组为5%（p < 0.001）。大多数便秘报告（72%）为轻度或中度，66%便秘患者的单次发作中位持续时间为8天。便秘在开始治疗后中位13天出现，可自行缓解、使用泻药后缓解或短暂中断治疗后缓解。阿洛司琼组4%（11/210）的患者和安慰剂组5%（28/640）的患者发生了严重不良事件。两名有心血管疾病既往危险因素的患者死亡；均未归因于研究药物。
每日两次服用1毫克阿洛司琼，持续12个月耐受性良好。便秘是最常见的不良事件，阿洛司琼治疗的患者中短暂性便秘发生率较高，通常发生在治疗的第一个月。
