A randomized, double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design.
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.
['Wigal|Timothy|T|', 'Brams|Matthew|M|', 'Frick|Glen|G|', 'Yan|Brian|B|', 'Madhoo|Manisha|M|']
D000293:Adolescent D000328:Adult D000662:Amphetamines D001289:Attention Deficit Disorder with Hyperactivity D000697:Central Nervous System Stimulants D018592:Cross-Over Studies D003692:Delayed-Action Preparations D004311:Double-Blind Method D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D011569:Psychiatric Status Rating Scales D017132:Workplace D055815:Young Adult
SHP465 mixed amphetamine salts duration of effect attention-deficit/hyperactivity disorder Adult workplace environment permanent product measure of performance ADHD rating scale time segment rating system ADHD self-rating scale