Findling Robert L, Wigal Sharon B, Bukstein Oscar G, Boellner Samuel W, Abikoff Howard B, Turnbow John M, Civil Rich
University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Clin Ther. 2009 Aug;31(8):1844-55. doi: 10.1016/j.clinthera.2009.08.002.
Short-term treatment with the meth-ylphenidate transdermal system (MTS) has been well tolerated in several clinical trials in children with attention-deficit/hyperactivity disorder (ADHD). However, the effects of long-term use have not been systematically evaluated.
The primary objective of this study was to assess the 12-month tolerability of MTS in children with ADHD. Effectiveness was a secondary objective.
This Phase III study was a multicenter, 12-month, open-label, flexible-dose extension of 4 previous trials. In those studies, children aged 6 to 12 years with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria) received MTS, osmotic-release oral system methylphenidate, or placebo. At entry into the present study, the children either continued to receive their optimal dose of MTS (10, 15, 20, or 30 mg per 9-hour patch wear time) or underwent dose titration over 4 weeks to an optimal MTS dose, which was continued for the remainder of the study. Tolerability was evaluated based on adverse events (AEs), physical examinations, vital signs, electrocardiograms, laboratory tests, the Children's Sleep Habits Questionnaire, and the occurrence of application-site reactions.
Of 327 enrolled subjects, 326 received treatment and 157 completed the study. The majority of enrolled subjects were male (64.8%) and white (73.7%), with a mean (SD) age of 9.2 (1.9) years. Two hundred sixty-five (81.3%) of the 326 subjects who received MTS reported AEs. AEs led to study discontinuation in 29 subjects (8.9%). The majority (98.3%) of treatment-emergent AEs were of mild or moderate severity. The most common AEs were decreased appetite (24.8%), headache (16.6%), upper respiratory tract infection (12.3%), cough (11.7%), pyrexia (10.1%), and decreased weight (10.1%). Of the 1118 AEs, 40.8% were considered possibly or probably related to study treatment. Three serious AEs (facial contusion, ankle fracture, and syncope) occurred and were considered unrelated to study treatment. Based on data collected across all study visits, application-site reactions generally consisted of mild erythema associated with mild discomfort at the patch site. Application-site reactions accounted for 22 (6.7%) study discontinuations.
Slightly less than half (48.0%) of subjects completed this 12-month, open-label extension study of MTS. Most AEs were mild to moderate in severity and, with the exception of application-site reactions, were typical of those previously observed with methylphenidate. ClinicalTrials.gov identifier: NCT00151957.
在多项针对注意力缺陷多动障碍（ADHD）儿童的临床试验中，甲基苯丙胺透皮系统（MTS）的短期治疗耐受性良好。然而，长期使用的效果尚未得到系统评估。
本研究的主要目的是评估MTS在ADHD儿童中的12个月耐受性。有效性是次要目的。
这项III期研究是对之前4项试验的多中心、12个月、开放标签、灵活剂量扩展研究。在那些研究中，年龄在6至12岁、诊断为ADHD（《精神疾病诊断与统计手册》第四版，修订版标准）的儿童接受了MTS、渗透释放口服系统甲基苯丙胺或安慰剂。在本研究开始时，儿童要么继续接受其最佳剂量的MTS（每9小时贴片佩戴时间10、15、20或30毫克），要么在4周内进行剂量滴定至最佳MTS剂量，并在研究的剩余时间内持续使用。根据不良事件（AE）、体格检查、生命体征、心电图、实验室检查、儿童睡眠习惯问卷以及应用部位反应的发生情况评估耐受性。
在327名登记受试者中，326名接受了治疗，157名完成了研究。登记受试者大多数为男性（64.8%）和白人（73.7%），平均（标准差）年龄为9.2（1.9）岁。在接受MTS的326名受试者中，265名（81.3%）报告了AE。AE导致29名受试者（8.9%）退出研究。大多数（98.3%）治疗中出现的AE为轻度或中度严重程度。最常见的AE是食欲下降（24.8%）、头痛（16.6%）、上呼吸道感染（12.3%）、咳嗽（11.7%）、发热（10.1%）和体重减轻（10.1%）。在1118例AE中，40.8%被认为可能或很可能与研究治疗有关。发生了3例严重AE（面部挫伤、踝关节骨折和晕厥），被认为与研究治疗无关。根据所有研究访视收集的数据，应用部位反应通常包括与贴片部位轻度不适相关的轻度红斑。应用部位反应导致22例（6.7%）退出研究。
略少于一半（48.0%）的受试者完成了这项为期12个月的MTS开放标签扩展研究。大多数AE严重程度为轻度至中度，除应用部位反应外，均为先前观察到的甲基苯丙胺典型反应。ClinicalTrials.gov标识符：NCT00151957。
