Clinical and Patient Global Impressions of Change Following Centanafadine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Pediatric Patients

Hypothesis/Objective: To evaluate the effect of centanafadine (CTN), a norepinephrine, dopamine, serotonin reuptake inhibitor, on ADHD symptoms and severity from two studies in pediatric patients with ADHD.
Methods: In two phase 3 trials (children [6-12y] and adolescents [13-17y]), patients were randomized to high-dose CTN, low-dose CTN, or placebo for 6 weeks; CTN dosing in children was weight-based. Change from baseline in Clinical Global Impression of Severity (CGI-S) at Week 6 and CGI of Change (CGI-C) and corresponding patient/caregiver-reported versions (PGI-S and PGI-C) were analyzed. CGI-S and PGI-S were analyzed via mixed models for repeated measures (last-observation-carried-forward). CGI-C and PGI-C were analyzed using van Elteren tests. P-values were not controlled for multiplicity and are descriptive.
Results: ADHD symptom severity at Week 6 was more improved with high-dose CTN versus placebo per the PGI-S in children (mean [95%CI] difference from placebo in change from baseline: −0.36 [−0.65, −0.08], P=0.0128) and adolescents (−0.29 [−0.55, −0.03], P=0.0282). The change in CGI-S was not evident in children, but clinicians perceived greater improvement in adolescents with high-dose CTN versus placebo (−0.37 [−0.61, −0.12], P=0.0038). At Week 6 in both studies, mean differences in PGI-C scores favored high-dose CTN versus placebo (children: −0.41 [−0.66, −0.17], P=0.0009; adolescents: −0.43 [−0.66, −0.20], P=0.0002), as did mean differences in CGI-C scores (children: −0.27 [−0.52, −0.02], P=0.0315; adolescents: −0.38 [−0.61, −0.14], P=0.0015).
Conclusions: High-dose CTN showed improvement versus placebo in the severity of ADHD symptoms in children and adolescents, with greater caregiver perception of severity improvement.