d-Amphetamine Transdermal System (d-ATS) in Treatment of Children and Adolescents With ADHD: SKAMP Score Analysis From a Pivotal Trial

Background The dextroamphetamine transdermal system (d-ATS) was developed as an alternative to current oral formulations of amphetamine, which is a first-line treatment for ADHD. In a randomized controlled trial of d-ATS in children and adolescents with ADHD, the primary endpoint (SKAMP total score) and secondary endpoints were met. This analysis evaluated the efficacy of d-ATS using SKAMP total score by optimized dose, gender, age group, ADHD type, and baseline ADHD severity. Methods This 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/9hr, with weekly evaluation for dose increase to 10 mg/9hr, 15 mg/9hr, and 20 mg/9hr. Once reached, the optimal dose was maintained for the DOP and used during the DBP. Preplanned subgroup analyses of mean SKAMP total score by optimized dose, gender, 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 score from a mixed-model repeated-measures (MMRM) analysis and is reported throughout as LS mean (95% confidence interval [CI]). Results In total, 110 patients were enrolled in the DOP, and 106 patients were randomized in the DBP. During the DOP, three patients reported 3 TEAEs that led to study discontinuation (irritability, appetite loss, abdominal pain). The difference (d-ATS vs placebo) in LS mean SKAMP total score was -5.9 (-6.8, -5.0), with differences in attention, deportment, and quality of work sub-scores of -1.4 (-1.7, -1.1), -1.9 (-2.2, -1.5), and -1.3 (-1.5, -1.0), respectively. Patients receiving d-ATS at each optimized dose demonstrated improvements vs placebo in LS mean SKAMP total score (-7.3 [-10.8, -3.7], -4.5 [-6.0, -3.0], -5.9 [-7.4, -4.5], -7.6 [-9.6, -5.6] at 5, 10, 15, and 20 mg/9hr, respectively). Both male and female patients experienced improvements vs placebo in SKAMP total score. The observed difference was greater in males (-6.3 [-7.3, -5.2]) vs females (-5.0 [-6.6, -3.4]). Similarly, improvements vs placebo were seen in patients with combined type ADHD and in those with predominantly inattentive type ADHD, with an observed LS mean difference of -8.0 (-9.2, -6.8) for the combined type and -3.3 (-4.6, -2.1) for the inattentive type. In addition, patients demonstrated improvement during the DBP regardless of baseline ADHD severity. The difference in LS mean SKAMP total score was -4.5 (-5.9, -3.1) for patients with a baseline SKAMP total score of 0-36 and -6.7 (-7.9, -5.6) for those with a baseline SKAMP score of 37-54. Conclusions d-ATS was effective and generally well-tolerated in treating ADHD in children and adolescents regardless of optimized dose, gender, age group, ADHD type, or baseline ADHD severity. Funding Noven Pharmaceuticals, Inc.