d-Amphetamine Transdermal System in Treatment of Children and Adolescents With ADHD: SKAMP Subscale Analysis and Subgroup Analysis from a Pivotal Trial.

Abstract

Objectives: d-Amphetamine transdermal system (d-ATS) is FDA-approved for treating attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients ≥6 years. In a pivotal study, d-ATS met its primary (SKAMP total score) and secondary endpoints. This analysis further evaluated d-ATS efficacy using SKAMP subscale scores and total score by subgroup.

Methods: The pivotal study comprised a 5-week, open-label dose-optimization period (DOP) followed by a 2-week, randomized, cross-over double-blind treatment period (DBP). All eligible patients received d-ATS 5 mg/9 h, with weekly evaluation for dose increase and the optimal dose maintained during the DBP. Preplanned subgroup analyses of mean SKAMP total score in the DBP by optimized dose, sex, age group, ADHD type, and baseline ADHD severity were conducted. Efficacy was assessed by difference (d-ATS vs. placebo) in least-squares (LS) mean SKAMP total and subscale scores (Attention, Deportment, and Quality of Work) from a mixed-model repeated-measures (MMRM) analysis and is reported throughout as LS mean (95% confidence interval [CI]). Model-based effect sizes were calculated post hoc.

Results: In total, 110 patients were enrolled in the DOP; 106 were randomized in the DBP. The LS mean difference in SKAMP total score of d-ATS versus placebo was -5.9 (-6.8, -5.0), with differences in subscale scores (Attention, Deportment, and Quality of Work) of -1.4 (-1.7, -1.1), -1.9 (-2.2, -1.5), and -1.3 (-1.5, -1.0), respectively. Model-based effect sizes were 0.57, 0.42, 0.43, and 0.47, respectively. Patients receiving d-ATS demonstrated improvements versus placebo in LS mean SKAMP total score at each optimized dose in both male and female patients and children and adolescents and regardless of ADHD subtype or baseline ADHD severity.

Conclusions: Consistent efficacy of d-ATS across subgroups and all SKAMP subscale scores suggests broad utility of d-ATS in all patients, regardless of age, sex, ADHD type, or baseline ADHD severity, and broad applicability of these results to patients with varying clinical presentations of functional impairment by ADHD.