(#4) Impact of Centanafadine on Executive Functioning in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder: Analysis of Conners 3 and Exit Survey Responses

Abstract: Objective: To compare the executive functioning (EF) efficacy measure with patient exit interviews in a pediatric population treated with centanafadine (CTN), a norepinephrine, dopamine, serotonin reuptake inhibitor for ADHD. Methods: Two phase 3 trials (NCT05428033 & NCT05257265) evaluated the efficacy and safety of once-daily extended-release CTN for ADHD treatment (aged 6-12y and 13-17y, respectively). Participants were randomized (1:1:1) to high-dose CTN, low-dose CTN, or placebo (children received weight-based CTN) for 6 weeks. A key secondary efficacy endpoint was the change from baseline in Conners 3-Parent Short EF content scale (containing 5 individual line items) T-score at Week 6, analyzed via a mixed-effect model for repeated measures. For the exit survey, values reflect those who selected either ìsomewhat betterî or ìmuch better.î All data reported here were collected via caregiver proxy. Results: Mean baseline EF T-scores were 74.4 in adolescents and 78.6 in children. In participants treated with high-dose CTN, a greater number of adolescents (48% vs 26%; P=0.0002) and children (40% vs 26%; P=0.0163) had a clinically meaningful change (?13-point reduction) in EF T-scores versus placebo. Per the caregiver-reported exit survey, of those treated with high-dose CTN, 71% (vs 43% placebo) of adolescents and 52% (vs 38% placebo) of children saw improvement in completing tasks at home. Similarly, 65% (vs 49% placebo) of adolescents and 50% (vs 38% placebo) of children saw improvement in completing work at school. Conclusions: Consistent with clinically meaningful change in EF, caregiver-reported perceptions of completing tasks at home and school showed improvement.Short Description: Executive functioning was measured via the Conners 3ñParent Short form assessment in a pediatric population treated for ADHD with centanafadineóa norepinephrine, dopamine, serotonin reuptake inhibitor. In participants treated with high-dose centanafadine, a greater number of adolescents and children had a clinically meaningful change in executive functioning T-scores when compared to placebo. Consistent with clinically meaningful change in executive functioning, caregiver-reported perceptions of completing tasks at home and in school showed improvement.Name of Sponsoring Organization(s): Otsuka Pharmaceutical Development & Commercialization, Inc.