A Randomized, Five-Way Crossover Study to Evaluate Bioequivalence of the Dextroamphetamine Transdermal System (d-ATS) at Five Application Sites in Healthy Adults

This work was sponsored by Noven Pharmaceuticals, Inc. Background: In a pivotal study, d-ATS applied to the hip met primary and secondary efficacy endpoints for ADHD in children and adolescents. Although no discontinuations resulting from application-site reactions occurred, site rotation may minimize dermal reactions, increasing tolerability. This study evaluated d-amphetamine pharmacokinetics and safety following d-ATS application across five application sites in healthy adults. Methods: In this open-label crossover study, healthy adults aged 18-45 were randomized to 1/5 left/right application sites (hip [reference], upper back, chest, upper arm, or flank) during each study period. One d-ATS patch (20mg/19.05cm²) was applied for 9 hours, with 7-day washout periods. Pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf) and dermal safety were assessed. To establish bioequivalence between application sites, 90% confidence intervals (CIs) for test-to-reference treatment ratios of the geometric means of Cmax, AUC0-t, and AUC0-inf must have been within FDA-specified limits of 80%-125%. Results: Demographics and baseline characteristics were balanced across treatment groups in the safety population (Nf50). All 90% CIs of test-to-reference ratios for Cmax, AUC0-t, and AUC0-inf were within 80%-125%. d-ATS-related erythema occurred in