a AVIDA Inc ., Newport Beach , CA , USA.
b Children's Developmental Center , Winter Park , FL , USA.
Postgrad Med. 2019 Apr;131(3):212-224. doi: 10.1080/00325481.2019.1574402. Epub 2019 Feb 18.
To evaluate the duration of efficacy, safety, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adolescents with attention-deficit/hyperactivity disorder (ADHD).
This phase 2, randomized, 3-period, 3-treatment crossover study compared SHP465 MAS (25/50 mg) with placebo and MAS IR (12.5 mg) in 13-17-year-old adolescents with ADHD having ADHD Rating Scale, Version IV (ADHD-RS-IV) total scores ≥24. A laboratory classroom served as a controlled environment during 16-hour observations, with efficacy assessed on the last day of each 7-day treatment period. The primary efficacy analysis compared SHP465 MAS with placebo on Permanent Product Measure of Performance (PERMP) total score averaged over the 16-hour postdose period using a mixed linear model. Comparisons were also conducted between MAS IR and placebo (for assay sensitivity) and between SHP465 MAS and MAS IR. PERMP problems attempted and answered correctly and ADHD symptoms based on ADHD-RS-IV; participant self-report; Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale; and Revised Conner's Parent Rating Scale scores were also evaluated. Safety and tolerability assessments included treatment-emergent adverse events and vital signs.
The intent-to-treat population included 84 participants. Least squares mean (95% CI) PERMP total score treatment differences significantly favored SHP465 MAS (combined 25/50 mg) over placebo for the average of all postdose assessment time points (41.26 [32.24, 50.29]; P < 0.0001) and each postdose assessment time point (all P < 0.0001). Similar results were observed for MAS IR versus placebo (all postdose assessment time points averaged: nominal P < 0.0001; each postdose assessment time point: all nominal P < 0.004). The safety and tolerability of SHP465 MAS were consistent with previous reports.
SHP465 MAS significantly improved PERMP total scores versus placebo from 2 to 16 hours postdose in adolescents with ADHD. The safety and tolerability profile of SHP465 MAS was consistent with previous reports of SHP465 MAS in individuals with ADHD.
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）在患有注意缺陷/多动障碍（ADHD）的青少年中的疗效持续时间、安全性和耐受性。
这是一项 2 期、随机、3 期、3 种治疗交叉研究，比较了 SHP465 MAS（25/50mg）与安慰剂和 MAS IR（12.5mg）在 ADHD 评定量表，第四版（ADHD-RS-IV）总分≥24 的 13-17 岁青少年中的疗效。在 16 小时观察期间，实验室教室作为一个对照环境，在每个 7 天治疗期的最后一天评估疗效。主要疗效分析采用混合线性模型比较 SHP465 MAS 与安慰剂在 16 小时给药后 PERMP 总分的平均值。还比较了 MAS IR 与安慰剂（用于测定灵敏度）以及 SHP465 MAS 与 MAS IR 之间的比较。还评估了基于 ADHD-RS-IV 的 PERMP 尝试和正确回答的问题数量和 ADHD 症状；参与者自我报告；斯旺森、科特金、阿格勒、M-Flynn 和佩勒姆量表；以及修订后的康纳父母评定量表的分数。安全性和耐受性评估包括治疗后出现的不良事件和生命体征。
意向治疗人群包括 84 名参与者。最小二乘均值（95%CI）PERMP 总分治疗差异在所有给药后评估时间点（41.26[32.24,50.29]）和每个给药后评估时间点（均 P<0.0001）均明显有利于 SHP465 MAS（联合 25/50mg）优于安慰剂。对于 MAS IR 与安慰剂，也观察到类似的结果（所有给药后评估时间点的平均值：名义 P<0.0001；每个给药后评估时间点：均名义 P<0.004）。SHP465 MAS 的安全性和耐受性与之前的报告一致。
SHP465 MAS 可显著改善 ADHD 青少年的 PERMP 总分，与安慰剂相比，从给药后 2 小时到 16 小时。SHP465 MAS 的安全性和耐受性与之前 SHP465 MAS 在 ADHD 患者中的报告一致。
