A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

ABSTRACT

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.

KEYWORDS:

• Adult workplace environment
• attention-deficit/hyperactivity disorder
• duration of effect
• SHP465 mixed amphetamine salts
• ADHD rating scale time segment rating system
• ADHD self-rating scale
• permanent product measure of performance

Supplemental data

Supplemental data for this article can be accessed here.

Acknowledgments

Under the direction of the authors, writing assistance was provided by Madhura Mehta, PhD, and Craig Slawecki, PhD (employees of Complete Healthcare Communications, LLC [CHC]; an ICON plc company, West Chester, PA). Editorial assistance in the form of proofreading, copyediting, and fact checking was also provided by CHC. Shailesh Desai, PhD, from Shire, reviewed and edited the manuscript for scientific accuracy. The authors would like to acknowledge Colleen Anderson, Med, for her contributions to the clinical development program for SHP465 MAS and for her insightful comments on this manuscript.

Declaration of interest

TW is a consultant to, member of the scientific advisory boards, has received speaker fees, and/or has received research support from, Akili, NLS Pharma, Tris Pharma, Ironshore, Neurovance, Novartis, Purdue, Rhodes, Shire, and Sunovion. MB has served as a speaker for Alkermes, Arbor, Lundbeck, NEOS, Otsuka, Rhodes, Shire, Silenor, Sunovion, Supernus, Takeda, Teva, and Tris; has received research support from Arbor, Shire, Teva, and Tris; and has served on advisory boards for NEOS, Otsuka, Shire, Supernus, Teva, and Tris. GF is a former employee of Shire and holds stock and/or stock options in Shire. BY and MM are employees of Shire and hold stock and/or stock options in Shire. Postgraduate Medicine peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Clinical research was funded by the sponsor, Shire Development LLC (Lexington, MA). Shire Development LLC provided funding to CHC, West Chester, PA) for support in writing and editing this manuscript.