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

Hypothesis/Objective: Evaluate caregiver and patient perspectives of the impact of centanafadine (CTN), a norepinephrine, dopamine, serotonin reuptake inhibitor, on learning problems (LP) in pediatric patients with ADHD.
Methods: In two phase 3 trials of children (6-12y) and adolescents (13-17y), patients 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) LP content scale T-scores (caregiver perspective for children/adolescents) and the Conners 3-Self-Report Short (SRS) LP content scale (adolescent perspective only), 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 LP 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], P=0.0393). No differences were observed for low-dose CTN in adolescents. Adverse events were generally mild to moderate.
Conclusions: In pediatric patients with ADHD, CTN was safe, well tolerated, and associated with greater caregiver- and patient-reported improvements in LP when compared to placebo.