A Randomized, Placebo-Controlled Study of the Efficacy and Safety of SHP465 Mixed Amphetamine Salts Extended-Release in Children and Adolescents With ADHD: Exploratory Analyses by Age

Objectives: To evaluate SHP465 mixed amphetamine salts (MAS) extended-release efficacy, safety, and tolerability by age group in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

Methods: This randomized, double-blind, placebo-controlled, dose-optimization study enrolled children (6–12 years old) and adolescents (13–17 years old) with DSM-IV-TR–defined ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Participants were randomized to SHP465 MAS (12.5 or 25 mg) or placebo. The primary efficacy endpoint (ADHD-RS-IV total score change from baseline to Week 4) was assessed using a linear mixed-effects model for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes.

Results: Least squares mean treatment differences (95% CI) in ADHD-RS-IV total score reductions from baseline to Week 4 favored SHP465 MAS over placebo in children (–12.0 [–17.3, –6.7]; effect size=0.93; nominal P<0.001) and adolescents (–8.7 [–12.6, –4.8]; effect size=0.72; nominal P<0.001). TEAE frequency was higher with SHP465 MAS than placebo in children (77.8% vs 46.2%) and adolescents (60.3% vs 46.8%); the most frequently reported TEAE (SHP465 MAS vs placebo) was decreased appetite (children, 42.6% vs 7.7%; adolescents, 21.8% vs 6.3%). At final on-treatment assessment, SHP465 MAS was associated with increases from baseline in pulse and blood pressure vs placebo in children and adolescents.

Conclusions: ADHD symptom improvement favored SHP465 MAS over placebo in both children and adolescents with ADHD. Overall safety and tolerability of SHP465 MAS in both age groups was generally consistent with the effects of other stimulants.