Evaluation of Dermal Irritation with the Dextroamphetamine Transdermal System (d-ATS) in Healthy Adults and Patients with ADHD

Background The d-ATS patch was developed as an alternative to oral amphetamine formulations for attention-deficit hyperactivity disorder (ADHD). The US Food & Drug Administration (FDA) recommends evaluating irritation of transdermal patches under intended (rotating application sites) and exaggerated use (repeated application to one site). These studies assessed irritation after d-ATS application. Methods Intended Use: In Study 1 , adults with ADHD, d-ATS was applied daily (9-hour application) for 4 weeks rotated between 5 sites (left/right: hip, flank, chest, upper arm, upper back), with irritation assessed on Days 1, 7, 14, 27, and 28. In Study 2 , children and adolescents with ADHD, d-ATS was applied daily (9 hours) for 5 weeks to the hip (left or right), with irritation assessed daily. Exaggerated Use: In Study 3 , adults with ADHD, d-ATS was applied daily (9 hours) to the hip (repeated application to one site) for 4 weeks, with irritation assessed daily. In Study 4 , healthy adults, 1 d-ATS and 1 placebo patch were applied daily (24 hours) for 21 days to the back (repeated application to 1 site), with irritation assessed daily. Irritation was assessed by a trained evaluator 30-60 min after patch removal using Berger and Bowman Dermal Response (0-7, with 7 being the worst reaction) and Other Effects (0-3, with 3 being the worst reaction) scores. Dermal Response and Other Effects scores were added together for the combined score. A combined score of ≥3 was considered clinically meaningful irritation. Results Intended Use: In Study 1 (N=15), meaningful irritation after patch removal was reported in 9/15 subjects (60%). The mean (SD) combined score was 1.05 (0.21), with no treatment-emergent adverse events at the application site. In Study 2 (N=110), all combined irritation scores were ≤3 for d-ATS, with a combined score of 3 reported by 2% of patients. There were no discontinuations due to dermal reactions in either study. Exaggerated Use: In Study 3 (N=20), meaningful irritation was reported in 19/20 subjects (95%). The mean (SD) combined score was 1.63 (0.78). In Study 4, mean (SD) combined scores were 2.1 (0.73) for d-ATS and 1.3 (0.69) for placebo (N=206 for both), with no discontinuations due to dermal reactions. Conclusions These results support previous findings that d-ATS is safe and well tolerated for ADHD. After intended use, irritation was minimal and did not cause study discontinuations. Funding Noven Pharmaceuticals, Inc.