Efficacy and Safety of Once-Daily Extended-Release Centanafadine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Pediatric Patients

Hypothesis/Objective: Evaluate the efficacy and safety of once-daily extended-release centanafadine (CTN), a norepinephrine, dopamine, serotonin reuptake inhibitor, for ADHD treatment in children (6-12y) and adolescents (13-17y).

Methods: In two phase 3 trials, patients were randomized to high-dose CTN, low-dose CTN, or placebo for 6 weeks; CTN dosing in children was weight-based. Endpoints included changes from baseline in ADHD-RS-5 symptoms total raw score (primary), CGI-S-ADHD, and Conners 3-Parent Short (PS) content scale T-scores at Week 6, analyzed via mixed model for repeated measures. Response rates were analyzed via a Cochran-Mantel-Haenszel test. Low-dose CTN did not meet the primary endpoint; therefore, P-values for secondary endpoints were not controlled for multiplicity and are descriptive. Safety and tolerability were assessed.

Results: The mean change (standard error [SE]) from baseline in ADHD-RS-5 score was greater for high-dose CTN versus placebo (children: −16.3[1.2] vs −10.8[1.2], P=0.0008; adolescents: −18.5[0.9] vs −14.2[0.9], P=0.0006). Greater mean change (SE) reductions in symptom severity per CGI-S-ADHD were observed with high-dose CTN versus placebo (children: −1.1[0.1] vs −0.9[0.1], P=0.0705; adolescents: −1.4[0.1] vs −1.1[0.1], P=0.0038). At the end of Week 6, more patients treated with high-dose CTN achieved a 30% improvement in response rate versus placebo (children: 44.8% vs 32.5%, P=0.0250; adolescents: 69.1% vs 50.3%, P=0.0013). In both studies, improvements in Conners 3-PS Inattention and

Hyperactivity/Impulsivity T-scores for high-dose CTN versus placebo were observed (P < 0.01, all comparisons). Most treatment-emergent adverse events were mild to moderate.

Conclusions: High-dose CTN was efficacious and generally well tolerated in the treatment of ADHD in this population.