A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Abstract

Objectives: To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys^™) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized, double-blind, dose-optimized laboratory classroom study. Methods: Children ages 6-12 with ADHD were enrolled. During a 3-week, open-label, Dose Optimization Phase, subjects initiated treatment with 39.2 mg/7.8 mg/day of SDX/d-MPH and were titrated weekly to an optimal dose (maximum dose of 52.3/10.4 mg). During the double-blind Treatment Phase, subjects were randomized to receive their optimal dose of SDX/d-MPH or placebo for 7 days. On day 7, efficacy was assessed in the laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). To evaluate safety, adverse events (AEs), vital signs, and electrocardiograms were assessed, and suicide risk was assessed. Results: A total of 149 subjects completed the study. In the primary efficacy analysis, the mean postdose change from baseline in SKAMP-Combined scores averaged over the laboratory classroom day was significantly improved with SDX/d-MPH versus placebo (least-squares mean treatment difference [95% confidence interval]: -5.41 [-7.10 to -3.71]; p < 0.001). A significant treatment effect for SDX/d-MPH compared with placebo was observed from 1 to 10 hours postdose. A post hoc analysis more comparable with that conducted in similar studies indicated a 0.5- to 13-hour onset and duration of efficacy. Both average postdose PERMP-Attempted and PERMP-Correct score changes from baseline were significantly improved among those treated with SDX/d-MPH versus placebo (p < 0.001 for both). No serious AEs were reported. During the Dose Optimization Phase, two-thirds of subjects reported AEs; the most common being insomnia and decreased appetite. Conclusions: SDX/d-MPH showed significant improvement in ADHD symptoms compared with placebo in children 6-12 years of age, with a rapid onset and extended duration of treatment effect. SDX/d-MPH was safe, with AEs comparable with those observed with other stimulant treatments.

Keywords: ADHD; SDX/d-MPH; pediatric.