The Time Course of Effect of Multilayer-Release Methylphenidate Hydrochloride Capsules: A Randomized, Double-Blind Study of Adults With ADHD in a Simulated Adult Workplace Environment

Abstract

PRC-063 significantly improved PERMP scores with an onset within 1 hr post-dose, and maintained improvement throughout the 16 hr post-dose study period compared with placebo in adults with ADHD.

Effects of SHP465 mixed amphetamine salts in adults with ADHD in a simulated adult workplace environment

“…The short-term safety and tolerability profile of 25 mg SHP465 MAS was generally consistent with previously published findings for SHP465 MAS in adults with ADHD [21][22][23] and for other long-acting stimulants assessed in adults within the AWE model [27,31]. The most frequently reported TEAEs (reported by ≥5% of participants) in this study included insomnia, decreased appetite, dry mouth, headache, and anorexia.…”

“…The frequency of insomnia-related TEAEs (initial insomnia, 1.3%; insomnia, 25.0%; middle insomnia, 1.3%; early morning awakenings, 1.3%) with 25 mg SHP465 MAS in the current study was similar to the frequency of insomnia-related TEAEs (combined preferred terms of insomnia, initial insomnia, middle insomnia, early morning awakenings, and terminal insomnia) reported in a phase III, dose-optimization study of SHP465 MAS (29.2% across all SHP465 MAS doses) [21] but was lower than the frequency reported in a phase III, forced-dose study of SHP465 MAS (40.4% with 25 mg SHP465 MAS) [22]. When comparing insomnia-related TEAEs occurring with SHP465 MAS in the current study with other long-acting psychostimulants in adults within the context of the AWE model [27,31], it is important to consider the use of a doseoptimization phase in the study designs. In the current study, which did not include a dose-optimization phase, the frequency of insomnia-related TEAEs with SHP465 MAS was higher than the frequencies reported for LDX (2.6%) and MLR-MPH (insomnia [6%] and initial insomnia [4%]) during the double-blind treatment phases that followed initial open-label dose-optimization phases of those studies [27,31].…”

“…As measured in this study, 25 mg SHP465 MAS produced significantly greater improvements in PERMP total score than placebo from 4 h postdose through 16 h postdose, which was the last time point measured. Although the magnitude of the overall treatment effect in the study was small, possibly due to a practice effect in both treatment groups that led to a small increase in PERMP scores across the day independent of treatment status, the mean PERMP total score changes from predose values averaged across all postdose time points in this study (approximate increases of 50 points with 25 mg SHP465 MAS and 22 points with placebo) were roughly comparable to the changes observed with LDX [27] and multilayer-release methylphenidate hydrochloride (MLR-MPH) [31] in the AWE model. The effects of 25 mg SHP465 MAS on secondary efficacy endpoints were generally consistent with the findings for PERMP total score, with the exception of the counselor-administered rating scale (Co-ADHD-RS TSRS).…”

“…When comparing insomnia-related TEAEs occurring with SHP465 MAS in the current study with other long-acting psychostimulants in adults within the context of the AWE model [27,31], it is important to consider the use of a doseoptimization phase in the study designs. In the current study, which did not include a dose-optimization phase, the frequency of insomnia-related TEAEs with SHP465 MAS was higher than the frequencies reported for LDX (2.6%) and MLR-MPH (insomnia [6%] and initial insomnia [4%]) during the double-blind treatment phases that followed initial open-label dose-optimization phases of those studies [27,31]. [27,31].…”

“…The PERMP is a time-sensitive, skilladjusted, 10-min math test that is administered following an 8-min level-finding test for proper placement [28]; it measures aspects of sustained attention, including the ability to initiate and perform effortful work, and stay on task, but not math ability [28]. The PERMP is considered a valid tool to investigate drug response and has been used in other studies evaluating efficacy in stimulants [27,[29][30][31].…”