University of California, Irvine, Child Development Center, Irvine, California, USA.
Child Adolesc Psychiatry Ment Health. 2010 Dec 14;4:32. doi: 10.1186/1753-2000-4-32.
Efficacy and safety profiles by sex and age (6-9 vs 10-12 years) and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX) vs placebo were assessed.
This study enrolled children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD) in an open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assessed interaction between sex or age and treatment and assessed effect sizes for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and Permanent Product Measure of Performance (PERMP) scales and ADHD Rating Scale IV measures. No corrections for multiple testing were applied on time points and subgroup statistical comparisons.
129 participants enrolled; 117 randomized. Both sexes showed improvement on all assessments at postdose time points; females showed less impairment than males for SKAMP and PERMP scores in treatment and placebo groups at nearly all times. Both age groups improved on all assessments at postdose time points. Children 10-12 years had less impairment in SKAMP ratings than those 6-9 years. Treatment-by-sex interactions were observed at time points for SKAMP-D, SKAMP total, and PERMP scores; no consistent pattern across scales or time points was observed. LDX demonstrated significant improvement vs placebo, by effect size, on SKAMP-D from 1.5-13 hours postdose. The overall LS mean (SE) SKAMP-D effect size was -1.73 (0.18). In the dose-optimization phase, common (≥2%) treatment-emergent adverse events (TEAEs) in males were upper abdominal pain, headache, affect lability, initial insomnia, and insomnia; in females were nausea and decreased weight. During the crossover phase for those taking LDX, higher incidence (≥2% greater) was observed in males for upper abdominal pain and insomnia and in females for nausea and headache. Overall incidence of TEAEs in age groups was similar.
Apparent differences in impairment level between sex and age groups were noted. However, these results support the efficacy of LDX from 1.5 hours to 13 hours postdose in boys and girls with medium to large effect sizes across the day with some variability in TEAE incidence by sex.
ClinicalTrials.gov Identifier: NCT00500149.
评估了性别和年龄（6-9 岁与 10-12 岁）以及 lisdexamfetamine dimesylate（LDX）与安慰剂相比的整体和全天效应大小的疗效和安全性特征。
这项研究招募了患有注意力缺陷/多动障碍（ADHD）的儿童（6-12 岁），进行了 LDX（30-70mg/d）的开放标签剂量优化，随后进行了随机、双盲、安慰剂对照、双向交叉阶段。事后分析评估了性别或年龄与治疗之间的相互作用，并评估了 Swanson、Kotkin、Agler、M-Flynn 和 Pelham（SKAMP）和永久性产品表现测量（PERMP）量表以及 ADHD 评定量表 IV 测量的效应大小。未对时间点和亚组统计比较进行多次检验校正。
共有 129 名参与者入组；117 名随机入组。两种性别在所有评估中都显示出了在给药后时间点的改善；在治疗和安慰剂组中，女性在 SKAMP 和 PERMP 评分方面的损害程度均低于男性，几乎所有时间点均如此。两个年龄组在所有评估中均显示出了在给药后时间点的改善。10-12 岁的儿童在 SKAMP 评分中的损害程度低于 6-9 岁的儿童。在 SKAMP-D、SKAMP 总分和 PERMP 评分的时间点观察到了治疗与性别之间的交互作用；没有观察到在各个时间点或时间点之间的一致模式。与安慰剂相比，LDX 在 SKAMP-D 上的疗效具有统计学意义，其效应大小为 1.5-13 小时。总体 LS 均值（SE）SKAMP-D 效应大小为-1.73（0.18）。在剂量优化阶段，男性常见（≥2%）的治疗相关不良事件（TEAEs）为上腹痛、头痛、情绪不稳定、初发性失眠和失眠；女性为恶心和体重下降。在服用 LDX 的交叉阶段，男性的上腹痛和失眠发生率更高（≥2%更高），女性的恶心和头痛发生率更高。不同年龄组的 TEAEs 总发生率相似。
注意到了性别和年龄组之间在损害程度上的明显差异。然而，这些结果支持 LDX 在 1.5 小时至 13 小时的疗效，且在全天的疗效大小为中到大型，在性别方面的 TEAEs 发生率存在一定的差异。
ClinicalTrials.gov 标识符：NCT00500149。
