Post hoc comparison of daily rates of nausea and vomiting with once- and twice-daily galantamine from a double-blind, placebo-controlled, parallel-group, 6-month study
Post hoc comparison of daily rates of nausea and vomiting with once- and twice-daily galantamine from a double-blind, placebo-controlled, parallel-group, 6-month study
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DOI：
10.1016/j.clinthera.2006.03.002
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Brashear, HR
中科院分区：
文献类型：
--
作者：
Dunbar, F;Zhu, Y;Brashear, HR
背景资料：与每日两次立即释放加兰他敏（GAL-IR）相比，每日一次延长释放加兰他敏（GAL-ER）制剂被设计成改善耐受性。目的：本研究的目的是对轻度至中度阿尔茨海默病（AD）受试者中GAL-ER与GAL-IR相比的恶心和呕吐的临床表现进行事后分析。这是一项在轻度至中度AD受试者中进行的以GAL-IR作为活性对照的GAL-ER大型、随机、双盲、安慰剂对照、多中心试验的事后分析报告。根据耐受性，加兰他敏剂量每4周滴定一次，增量为8 mg/d，每日剂量为16或24 mg。比较GAL-ER和GAL-IR组的恶心和呕吐每日发生率。计算剂量滴定期间报告恶心/呕吐的受试者每日百分比的AUC。恶心/呕吐止吐药的使用进行了比较GAL-ER和GAL-IR groups.Results：GAL-ER，GAL-IR，安慰剂组之间的人口统计学特征相似。16.9%（54/319）的GAL-ER、13.8%（45/326）的GAL-IR和5.0%（16/320）的安慰剂患者报告了恶心; 6.6%（21/319）的GAL-ER、8.6%（28/326）的GAL-IR和2.2%（7/320）的安慰剂患者报告了呕吐。总人群中恶心的平均（SD）日发生率为3.1% GAL-ER组为13.43%，GAL-IR组为22.07%（P = NS）; GAL-ER组和GAL-IR组总人群的平均（SD）每日呕吐率分别为0.6%（4.14%）和1.6%（14.50%）（P = NS）。安慰剂组总人群中恶心或呕吐的平均（SD）每日发生率分别为1.2（8.46）和0.4（5.44）。对于报告恶心的受试者，GAL-ER组恶心天数的平均（SD，SE）百分比低于GAL-IR组（18. 4%[28. 22%，5. 31%] vs 38. 0%[48. 23%，6. 04%]; P = 0. 014）。GAL-IR组在剂量滴定期间报告恶心/呕吐的受试者每日百分比的AUC显著高于安慰剂组（320.9 vs 102.9; P = 0.01）; GAL-ER组与安慰剂组之间无统计学差异（171.1 vs 102.9; P = NS）。GAL-ER组报告恶心或呕吐的受试者使用止吐药的比例显著低于GAL-IR组（33.3% vs 53.4%; P 0.028）。结论：在这些AD受试者中，GAL-ER组和GAL-IR组报告恶心和呕吐的受试者每日百分比以及报告呕吐的受试者中呕吐天数百分比无显著差异。然而，在报告恶心的受试者中，GAL-ER与恶心天数百分比显著低于GAL-IR相关。剂量滴定期间GAL-ER组和安慰剂组之间恶心或呕吐受试者每日百分比的AUC无显著差异，但GAL-IR组显著高于安慰剂组。恶心或呕吐的受试者接受GAL-ER报告的止吐药使用显著少于GAL-IR治疗的受试者。这些结果表明，需要进行额外的研究，以探讨这些制剂耐受性的潜在差异。
Background: A once-daily extended-release galantamine (GAL-ER) formulation has been designed to improve tolerability compared with twice-daily immediate-release galantamine (GAL-IR).Objective: The aim of this study was to conduct a post hoc analysis of the clinical presentation of nausea and vomiting with GAL-ER compared with GAL-IR in subjects with mild to moderate Alzheimer's disease (AD).Methods: This is the report of a post hoc analysis of a large, randomized, double-blind, placebo-controlled, multicenter trial of GAL-ER with GAL-IR as the active control in subjects with mild to moderate AD. Galantamine dose was titrated every 4 weeks by increments of 8 mg/d to a daily dose of 16 or 24 mg, based on tolerability. Daily rates of nausea and vomiting were compared for the GAL-ER and GAL-IR groups. AUCs of the daily percentage of subjects reporting nausea/vomiting during dose titration were calculated. Antiemetic use for nausea/vomiting was compared between GAL-ER and GAL-IR groups.Results: Demographic characteristics were similar between the GAL-ER, GAL-IR, and placebo groups. Nausea was reported by 16.9% (54/319) of GAL-ER, 13.8% (45/326) of GAL-IR, and 5.0% (16/320) of placebo patients; vomiting was reported for 6.6% (21/319) of GAL-ER, 8.6% (28/326) of GAL-IR, and 2.2% (7/320) of placebo patients. The mean (SD) daily rate of nausea in the total population was 3.1% (13.43%) in the GAL-ER group and 5.2% (22.07%) in the GAL-IR group (P = NS); the mean (SD) daily rate of vomiting for the total population was 0.6% (4.14%) in the GAL-ER group and 1.6% (14.50%) in the GAL-IR group (P = NS). The mean (SD) daily rate of nausea or vomiting in the total population was 1.2 (8.46) and 0.4 (5.44) in the placebo group, respectively. For subjects reporting nausea, the mean (SD, SE) percentage of days with nausea was lower with GAL-ER than with GAL-IR (18.4% [28.22%, 5.31%] vs 38.0% [48.23%, 6.04%]; P = 0.014). AUC of the daily percentage of subjects reporting nausea/vomiting during dose titration was significantly higher in the GAL-IR group compared with the placebo group (320.9 vs 102.9; P = 0.01); there was no statistical difference between the GAL-ER group and placebo (171.1 vs 102.9; P = NS). Antiemetic use by subjects reporting nausea or vomiting was significantly lower in the GAL-ER group than the GAL-IR group (33.3% vs 53.4%; P 0.028).Conclusions: In these subjects with AD, the daily percentage of subjects reporting nausea and vomiting, and the percentage of days with vomiting among subjects reporting vomiting, did not significantly differ between the GAL-ER and GAL-IR groups. However, GAL-ER was associated with a significantly lower percentage of days with nausea than GAL-IR among subjects reporting nausea. AUC of the daily percentage of subjects with nausea or vomiting during dose titration did not differ significantly between the GAL-ER and placebo groups but was significantly higher in the GAL-IR group than placebo. Subjects with nausea or vomiting who received GAL-ER reported significantly less antiemetic use than those treated with GAL-IR. These results suggest the need for additional studies to explore the potential differences in the tolerability of these formulations.