Efficacy and Safety of Trimodal Dexmethylphenidate (CTx-1301) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Results From a Phase 3, Randomized, Double-Blind, Fixed-Dose, Placebo-Controlled Trial

Background: CTx-1301 is the first trimodal dexmethylphenidate formulation developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods: In this 5-week, phase 3, fixed-dose study, patients with ADHD aged 6–17 years were randomized to once-daily treatment with CTx-1301 (18.75, 25.0, or 37.5 mg) or placebo. CTx-1301 was initiated at 12.5 mg and uptitrated weekly to reach the assigned fixed dose. The primary endpoint was the change from baseline to week 5 in the ADHD Rating Scale, Version 5 (ADHD-RS-5). Secondary efficacy endpoints included Clinical Global Impression–Severity (CGI-S) and –Improvement (CGI-I). Statistical comparisons were evaluated at a Bonferroni-adjusted significance level of 0.017. Results: The mean age (±standard deviation) of the study population ( N = 103) was 11.3 ± 3.3 years, and the majority of subjects (60.2%) were male. Treatment with CTx-1301 25.0 or 37.5 mg significantly improved ADHD-RS-5 score from baseline compared with placebo ( p ≤ 0.011). Exploratory post hoc analyses revealed effect sizes for the comparison of CTx-1301 and placebo ranging from 0.732 (18.75-mg dose) to 1.185 (37.5-mg dose). Improvement in CGI-S was statistically significant for CTx-1301 37.5 mg versus placebo ( p < 0.001). More than 60% of subjects who received CTx-1301 were much to very much improved on CGI-I compared with 18% for placebo. All adverse events were mild or moderate in severity, no new safety signals were identified, and the safety profile was consistent with the known effects of dexmethylphenidate. Conclusions: CTx-1301 demonstrated dose-related improvements in signs and symptoms of ADHD, although statistical significance is not consistent across all dose groups. The treatment was well tolerated over 5 weeks in children and adolescents with ADHD. Given the limited sample size and reduced statistical power, these findings should be considered preliminary and require confirmation in larger, adequately powered studies.