Efficacy and Safety of Centanafadine for ADHD Treatment in Children: A Randomized Clinical Trial

BACKGROUND AND OBJECTIVES Centanafadine (CTN) is a first-in-class norepinephrine, dopamine, serotonin reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder (ADHD). This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy, safety, and tolerability of CTN vs placebo in children with ADHD. METHODS Children aged 6 to 12 years (inclusive) with a primary diagnosis of ADHD were randomized to weight-based low-dose CTN, weight-based high-dose CTN, or placebo once daily for 6 weeks. The primary endpoint was the change from baseline in the ADHD Rating Scale, version 5 (ADHD-RS-5) symptoms total raw score at week 6. RESULTS Of 480 participants randomized (low-dose CTN, n = 154; high-dose CTN, n = 162; placebo, n = 164), 457 received at least 1 dose of study drug and 367 (76%) completed the trial. At week 6, improvements in ADHD-RS-5 symptoms total raw score were significantly greater with high-dose CTN than with placebo (–16.3 [1.2] vs –10.8 [1.2], P < .001). High-dose CTN showed separation from placebo as early as week 1, the first postbaseline time point, with the effect maintained throughout the study period. Low-dose CTN did not show statistical significance in the primary endpoint. Treatment-emergent adverse events (TEAEs) occurred in 52/147 (35%) participants in the low-dose CTN group, 61/157 (39%) in the high-dose CTN group, and 39/153 (25%) in the placebo group. The most common TEAEs were decreased appetite (23/457 [5%]), rash (14/457 [3%]), and vomiting (13/457 [3%]). All TEAEs were of mild or moderate severity. CONCLUSIONS High-dose CTN was efficacious for treatment of ADHD in children. Both CTN doses were safe and well tolerated.