797 - Improvement in Caregiver-Rated Executive Functioning Following Centanafadine Treatment in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder

Publication Number: 797.5379

Caroline L. Ward, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, United States, Rockville, MD, United States; Judy van Stralen, Center for Pediatric Excellence, Ottawa, ON, Canada; Ann C. Childress, Center for Psychiatry and Behavioral Medicine, Inc, Las Vegas, NV, United States; Taisa R. Skubiak, Otsuka, Fairfield, CT, United States; Na Jin, Otsuka, Rockville, MD, United States; Timothy E.. Wilens, NIH (NIDA), BOSTON, MA, United States; Dorothee Oberdhan, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, United States, Rockville, MD, United States

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common pediatric neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Individuals with ADHD can also have impairments in executive functioning or high-level cognitive processes that include inhibition, switching between tasks, working memory, planning, monitoring, and verbal and design fluency. Two phase 3 trials evaluated the efficacy and safety of once-daily extended-release centanafadine (CTN), a norepinephrine, dopamine, serotonin reuptake inhibitor, for the treatment of ADHD in children and adolescents.

Objective: To evaluate the impact of CTN on executive functioning in pediatric patients with ADHD

Design/Methods: In two phase 3 trials (children [6–12 years] and adolescents [13–17 years]), eligible patients with a primary diagnosis of ADHD (of any presentation) according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria, as confirmed by the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) were randomized (1:1:1) to high-dose CTN, low-dose CTN, or placebo for 6 weeks; CTN dosing in children was weight-based. A key secondary efficacy endpoint in both studies was the change from baseline in Conners 3–Parent Short (PS) Executive Functioning Content Scale T-score at Week 6. Data presented here reflect the caregiver perspective and were analyzed via a mixed model for repeated measures. P-values are not controlled for multiplicity and are considered descriptive. Safety and tolerability were assessed.

Results: In patients treated with high-dose CTN, a greater difference than placebo in the mean change from baseline at Week 6 in Executive Functioning T-score was observed for both children (mean change [standard error]: CTN, −11.3 [1.12]; placebo, −6.8 [1.11], P=0.0026) and adolescents (CTN, −13.0 [1.01]; placebo, −8.1 [0.99], P=0.0003). Significant improvements with high-dose CTN versus placebo were observed as early as Week 1 in children (P=0.0073) and Week 2 in adolescents (P=0.0047), with effects sustained or further improved with continued treatment. Adverse events were generally mild to moderate. CTN was generally safe and well tolerated.

Conclusion(s): In pediatric patients with ADHD, high-dose CTN was efficacious at Week 6 in the Conners 3–PS Executive Functioning Content Scale and was generally well tolerated.