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 (N&#3f50). 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 3% of subjects, with no marked differences between application sites. No subject reported more than moderate discomfort, with most reporting mild or no discomfort, and minimal irritation. No new safety concerns were identified. Conclusions: In this study, bioequivalence between all d-ATS application sites tested was observed. No new safety concerns were identified, with comparable dermal findings across sites. With bioequivalence across sites, patients can choose from 10 d-ATS application sites (including left/right sides) to minimize dermal reactions.