Efficacy and Safety of Dextroamphetamine Transdermal System for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results from a Pivotal Phase 2 Study

Abstract

Objectives: To assess efficacy and safety of the new Dextroamphetamine Transdermal System (d-ATS) to treat children and adolescents (aged 6-17 years) with attention-deficit/hyperactivity disorder (ADHD). Methods: In this phase 2, randomized, placebo-controlled study, 4 d-ATS patches of differing doses (5, 10, 15, and 20 mg) were evaluated. Patients began a 5-week, open-label, stepwise dose-optimization period in which they received a 5-mg d-ATS patch (applied to hip) for 9 hours. During weekly visits, patients were evaluated for possible adjustments to the next dose level based on efficacy and safety. Once at the optimal dose, that dose was maintained during a 2-week, crossover double-blind treatment period. Primary endpoint was to assess efficacy of d-ATS versus placebo as measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) total score; key secondary endpoints included assessing onset and duration of efficacy by SKAMP total score, and additional secondary endpoints included Permanent Product Measure of Performance (PERMP) scores. Safety was assessed throughout. Results: d-ATS treatment resulted in significant improvements versus placebo in ADHD symptoms as measured by SKAMP total score, with overall least-squares mean difference (95% confidence interval) versus placebo of -5.87 (6.76, -4.97; p < 0.001) over the 12-hour assessment period. Onset of efficacy was observed at 2 hours postdose (p < 0.001), and duration of effect continued through 12 hours (patch removed at 9 hours), with significant differences between d-ATS and placebo at all time points from 2 hours onward (all p ≤ 0.003). Significant improvements versus placebo in PERMP-A and PERMP-C scores were also observed from 2 to 12 hours postdose with d-ATS treatment. d-ATS was safe and well-tolerated, with a systemic safety profile similar to that observed with oral amphetamines. Conclusions: This study demonstrates that d-ATS is an effective and well-tolerated treatment for children and adolescents with ADHD. These data indicate that d-ATS can deliver sustained levels of efficacy along with the advantages of transdermal drug delivery, making it a beneficial new treatment option. Clinical Trial Registration no.: NCT01711021.

Keywords: ADHD; clinical trial; dextroamphetamine; transdermal.

FIG. 1.

Study design. Visit numbers also correspond to week number.

FIG. 2.

Optimized d-ATS doses for (A) all randomized patients, (B) those aged 6–12 years, and (C) those aged 13–17 years (dose-optimization period). d-ATS, dextroamphetamine transdermal system.

FIG. 3.

Time course of SKAMP total scores during laboratory classroom assessment (full analysis set). *p < 0.05; ^†p < 0.001. CI, confidence interval; LS, least-squares; SE, standard error; SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale.

FIG. 4.

PERMP (A) number of problems attempted by time and (B) number of problems correct by time during the double-blind treatment period (full analysis set). ^†p < 0.001. LS, least squares; PERMP, Permanent Product Measure of Performance; SE, standard error.

FIG. 5.

Patch wear time simulation: median PK and SKAMP score over time in children and adolescents. PK, pharmacokinetic; SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale.