Biederman Joseph, Krishnan Suma, Zhang Yuxin, McGough James J, Findling Robert L
Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Clin Ther. 2007 Mar;29(3):450-63. doi: 10.1016/s0149-2918(07)80083-x.
Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. It was developed with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Following ingestion, the pharmacologically active d-amphetamine molecule is gradually released by rate-limited hydrolysis.
The aims of this study were to assess the efficacy and tolerability of LDX in school-aged children with attention-deficit/hyperactivity disorder (ADHD) treated in the community, and to characterize the duration of action of LDX compared with placebo.
This Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study was conducted at 40 centers across the United States. Male and female children aged 6 to 12 years with ADHD were randomly assigned to receive LDX 30, 50, or 70 mg with forced-dose titration, or placebo, PO QD for 4 weeks. Efficacy was assessed using the ADHD Rating Scale Version IV (ADHD-RS-IV), the Conners' Parent Rating Scale (CPR'), and the Clinical Global Impression of Improvement scale. Tolerability was assessed throughout the study.
Of the 290 randomized patients (201 boys, 89 girls; mean [SD] age, 9 [1.8] years), 230 completed the trial (LDX 30 mg, n=56; LDX 50 mg, n=60; LDX 70 mg, n=60; and placebo, n=54). The most common reasons for study discontinuation (n=60) were lack of efficacy (LDX 30 mg, 1%; LDX 50 mg, 0%; LDX 70 mg, 1 %; and placebo, 17%) and adverse events (AEs) (LDX 30 mg, 9%; LDX 50 mg, 5%; LDX 70 mg, 14%; and placebo, 1%). Significant improvements in ADHD-RS-IV scores were seen with all doses of LDX compared with placebo (all, P<0.001), and in CPRS scores with all LDX doses versus placebo throughout the day (all, P<0.001 for all comparisons). Efficacy was observed by the first week of treatment, and improvements were observed throughout the day up to approximately 6 PM. The most frequently reported AEs among patients receiving LDX were typical of amphetamine products: decreased appetite (39% with active treatment vs 4% with placebo), insomnia (19% vs 3%), upper abdominal pain (12% vs 6%), headache (12% vs 10%), irritability (10% vs 0%), vomiting (9% vs 4%), weight decrease (9% vs 1%), and nausea (6% vs 3%); most were mild to moderate and occurred in the first week.
In this population of children with ADHD, treatment once daily with the prodrug LDX at doses of 30 to 70 mg appeared to be effective and had a tolerability profile similar to those of currently marketed extended-release stimulants.
赖右苯丙胺二甲磺酸盐（LDX）是一种无治疗活性的苯丙胺前体药物。其研发目的是提供持续一整天的延长作用时间，同时降低滥用、过量毒性和药物篡改的可能性。摄入后，具有药理活性的d - 苯丙胺分子通过限速水解逐渐释放。
本研究旨在评估LDX在社区治疗的注意力缺陷/多动障碍（ADHD）学龄儿童中的疗效和耐受性，并与安慰剂相比，描述LDX的作用持续时间。
这项III期、多中心、随机、双盲、强制剂量、平行组研究在美国40个中心进行。年龄6至12岁的ADHD男性和女性儿童被随机分配接受30、50或70mg的LDX并进行强制剂量滴定，或接受安慰剂，每日口服一次，共4周。使用ADHD评定量表第四版（ADHD - RS - IV）、康纳斯父母评定量表（CPR'）和临床总体印象改善量表评估疗效。在整个研究过程中评估耐受性。
290名随机分组的患者（201名男孩，89名女孩；平均[标准差]年龄，9[1.8]岁）中，230名完成了试验（LDX 30mg组，n = 56；LDX 50mg组，n = 60；LDX 70mg组，n = 60；安慰剂组，n = 54）。研究中止的最常见原因（n = 60）是缺乏疗效（LDX 30mg组为1%；LDX 50mg组为0%；LDX 70mg组为1%；安慰剂组为17%）和不良事件（AE）（LDX 30mg组为9%；LDX 50mg组为5%；LDX 70mg组为14%；安慰剂组为1%）。与安慰剂相比，所有剂量的LDX在ADHD - RS - IV评分上均有显著改善（所有P < 0.001），并且在全天的CPRS评分上，所有LDX剂量与安慰剂相比均有改善（所有比较P < 0.001）。在治疗的第一周就观察到了疗效，并且在直至下午6点左右的全天都观察到了改善。接受LDX治疗的患者中最常报告的AE是苯丙胺类产品常见的：食欲减退（活性治疗组为39%，安慰剂组为4%）、失眠（19%对3%）、上腹部疼痛（12%对6%）、头痛（12%对10%）、易怒（10%对0%）、呕吐（9%对4%）、体重减轻（9%对1%）和恶心（6%对3%）；大多数为轻度至中度，且发生在第一周。
在这群ADHD儿童中，每日一次使用30至70mg剂量的前体药物LDX治疗似乎有效，并且耐受性与目前市场上销售的缓释兴奋剂相似。
