一项使用模拟成人工作场所设计的、评估 SHP465 混合安非他命盐长效片治疗成人 ADHD 的随机、双盲研究。
A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design.
机构信息
a AVIDA Inc ., Newport Beach , CA , USA.
b Department of Psychiatry & Behavioral Sciences , Baylor College of Medicine , Houston , TX , USA.
出版信息
Postgrad Med. 2018 Jun;130(5):481-493. doi: 10.1080/00325481.2018.1481712. Epub 2018 Jun 18.
OBJECTIVES
The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).
METHODS
Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.
RESULTS
Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS-placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.
CONCLUSIONS
SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.
目的
本文旨在评估 SHP465 混合安非他命盐（MAS）缓释制剂与安慰剂和即时释放 MAS（MAS IR）在成人注意力缺陷/多动障碍（ADHD）患者中的疗效、作用持续时间和耐受性。
方法
采用 ADHD 评定量表第四版（ADHD-RS-IV）评分≥24 的成人，在模拟成人工作场所环境中，采用双盲、三周期交叉研究，按 50 或 75mg SHP465 MAS、安慰剂或 25mg MAS IR 进行随机分组。在每个 7 天治疗期的最后一天，在给药后 16 小时进行疗效评估。采用混合线性模型，在意向治疗人群中对所有给药后评估和每个给药后时间点的永久产品绩效测量（PERMP）总分进行主要疗效分析。次要终点包括 PERMP 尝试和正确回答的问题数量，以及基于顾问使用时间片段评分系统和参与者自我报告对咨询师观察的临床医生评分的 ADHD-RS-IV 评分。耐受性评估包括治疗中出现的不良事件（TEAEs）和生命体征。
结果
最小二乘均值（95%置信区间）治疗差异（合并 50/75mg SHP465 MAS-安慰剂）显示，SHP465 MAS 优于安慰剂，用于所有给药后评估的 PERMP 总分（18.38[11.28, 25.47]；P<0.0001）和每个给药后评估（均 P<0.02）。MAS IR 优于安慰剂的 PERMP 总分平均优势在名义上是显著的（名义 P=0.0001）；SHP465 MAS 和 MAS IR 之间的治疗差异不显著（名义 P=0.2443）。与 SHP465 MAS 相关的最常报告的两种不良事件是失眠（36.5%）和厌食（21.2%）。SHP465 MAS 引起的脉搏和血压平均升高超过安慰剂。
结论
SHP465 MAS（合并 50/75mg）与安慰剂相比显著提高了 PERMP 总分，在给药后 2 至 16 小时观察到优势。SHP465 MAS 的耐受性与之前报道的成人 ADHD 中 SHP465 MAS 相似。
临床试验注册
https://clinicaltrials.gov/ct2/show/NCT00928148，标识符为 NCT00928148。
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