796 - Efficacy of Centanafadine on the Conners 3 Learning Problems Content Scale in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder

Publication Number: 796.4923

Dorothee Oberdhan, 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; Caroline L. Ward, 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, all of which can affect the process of learning. 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: Evaluate caregiver and patient perspectives of the impact of CTN on learning problems in pediatric patients with ADHD

Design/Methods: In two phase 3 trials of 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 to high-dose CTN, low-dose CTN, or placebo for 6 weeks; dosing in children was weight-based. Presented here is the change from baseline in Conners 3–Parent Short (PS) Learning Problems Content Scale (caregiver perspective for children/adolescents) and the Conners 3–Self-Report Short (SRS) Learning Problems Content Scale (adolescent perspective only) T-scores, analyzed via a mixed-effect model for repeated measures. P-values are descriptive and not controlled for multiplicity. Safety and tolerability were also assessed.

Results: Overall, 76.5% (367/480) of children (mean age 9.2y, 58.3% male) and 80.8% (371/459) of adolescents (mean age 14.7y, 59.3% male) completed their respective studies. At Week 6 a significant mean change from baseline in Learning Problems Content Scale T-scores was observed with high-dose CTN compared to placebo in children (mean change [standard error]: −8.2 [0.95] vs placebo −2.8 [0.93], P< 0.0001) and in adolescents (PS: −8.0 [0.92] vs placebo −3.1 [0.90], P< 0.0001; SRS: −6.1 [0.86] vs placebo −2.5 [0.85], P=0.0023). Low-dose CTN also demonstrated a significant effect compared to placebo at Week 6 in children (−5.47 [0.97] vs placebo −2.81 [0.93], P=0.0393). No differences were observed for low-dose CTN in adolescents. Adverse events were generally mild to moderate.

Conclusion(s): In pediatric patients with ADHD, CTN was safe, well tolerated, and associated with greater caregiver- and patient-reported improvements in learning problems when compared to placebo.