Wigal Timothy, Childress Ann, Frick Glen, Yan Brian, Wigal Sharon, Madhoo Manisha
a AVIDA Inc. , Newport Beach , CA , USA.
b Center for Psychiatry and Behavioral Medicine , Las Vegas , NV , USA.
Postgrad Med. 2018 Jan;130(1):111-121. doi: 10.1080/00325481.2018.1389227. Epub 2017 Oct 31.
Evaluate the efficacy, duration of effect, and safety of 25 mg SHP465 mixed amphetamine salts (MAS) extended-release versus placebo in adults with attention-deficit/hyperactivity disorder (ADHD).
Adults (18-55 years) with ADHD and with ADHD Rating Scale-IV (ADHD-RS-IV) scores ≥24 were randomized to treatment in a double-blind, 2-period, 2-treatment crossover study utilizing the Adult Workplace Environment (AWE), as described by Wigal and Wigal (J Atten Disord 2006;10:92-111). On day 7 of each 7-day treatment period, efficacy was assessed during a 16.5-hour postdose period. The primary endpoint, Permanent Product Measure of Performance (PERMP) total score, was analyzed in the intent-to-treat population using a mixed linear model of analysis of variance. Secondary endpoints, for which the study was not powered, included PERMP problems attempted and answered correctly, ADHD clinician ratings based on counselor observations and inputs during the Time Segment Rating System (Co-ADHD-RS TSRS), and the ADHD self-rating scale (ADHD-SRS). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.
The least squares mean (95% CI) treatment difference (SHP465 MAS-placebo) for PERMP total score significantly favored SHP465 MAS over placebo when averaged across all postdose assessments (19.29 [10.95, 27.63]; P < 0.0001), with significant treatment differences favoring SHP465 MAS over placebo observed at 4-16 hours postdose (all P < 0.01). TEAEs observed with SHP465 MAS (≥5% of participants) included insomnia, decreased appetite, dry mouth, headache, and anorexia. Mean pulse and blood pressure increases with SHP465 MAS exceeded those of placebo.
SHP465 MAS (25 mg) was superior to placebo on PERMP total score, with treatment differences observed from 4 to 16 hours postdose; nominal treatment differences on the ADHD-SRS, but not the Co-ADHD-RS TSRS, were also observed. The safety and tolerability profile of SHP465 MAS was similar to previous reports for SHP465 MAS and other long-acting stimulants. Clinical trials registry: clinicaltrials.gov (NCT00202605; https://clinicaltrials.gov/ct2/show/NCT00202605 ).
评估25毫克SHP465混合安非他明盐（MAS）缓释剂与安慰剂相比，对患有注意力缺陷多动障碍（ADHD）的成年人的疗效、作用持续时间和安全性。
ADHD评分量表-IV（ADHD-RS-IV）得分≥24的18至55岁ADHD成年人，在一项双盲、两阶段、两种治疗的交叉研究中被随机分配接受治疗，该研究采用了Wigal和Wigal描述的成人工作场所环境（AWE）（《注意力障碍杂志》2006年；10：92-111）。在每个7天治疗期的第7天，在给药后16.5小时期间评估疗效。主要终点，即永久绩效产品测量（PERMP）总分，在意向性治疗人群中使用混合线性方差分析模型进行分析。次要终点（该研究未针对这些终点进行效力计算）包括尝试并正确回答的PERMP问题、基于咨询师在时间段评分系统（联合ADHD-RS TSRS）期间的观察和输入得出的ADHD临床医生评分，以及ADHD自评量表（ADHD-SRS）。安全性和耐受性评估包括治疗中出现的不良事件（TEAE）和生命体征。
当对所有给药后评估进行平均时，PERMP总分的最小二乘均值（95%CI）治疗差异（SHP465 MAS-安慰剂）显著有利于SHP465 MAS而非安慰剂（19.29 [10.95, 27.63]；P < 0.0001），在给药后4至16小时观察到有利于SHP465 MAS而非安慰剂的显著治疗差异（所有P < 0.01）。SHP465 MAS观察到的TEAE（≥5%的参与者）包括失眠、食欲减退、口干、头痛和厌食。SHP465 MAS导致的平均脉搏和血压升高超过安慰剂。
SHP465 MAS（25毫克）在PERMP总分上优于安慰剂，在给药后4至16小时观察到治疗差异；在ADHD-SRS上也观察到名义上的治疗差异，但在联合ADHD-RS TSRS上未观察到。SHP465 MAS的安全性和耐受性概况与之前关于SHP465 MAS和其他长效兴奋剂的报告相似。临床试验注册：clinicaltrials.gov（NCT00202605；https://clinicaltrials.gov/ct2/show/NCT00202605 ）
