52-Week Open-Label Safety and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder

This trial was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Introduction: Centanafadine (CTN) is a novel norepinephrine/dopamine/serotonin reuptake inhibitor in development for attention-deficit/hyperactivity disorder (ADHD). In 2 pivotal phase 3 adult ADHD trials, CTN sustained release (SR) 200 and 400 mg total daily dose (TDD), administered in 2 doses daily (BID), significantly reduced Adult ADHD Investigator Symptom Rating Scale (AISRS) total score vs placebo, with favorable safety and tolerability. Long-term effects of treatment with CTN SR 400 mg TDD in patients with adult ADHD (NCT03605849) are reported. Methods: Adults meeting DSM-5 criteria for ADHD who completed a pivotal trial or enrolled de novo were eligible for this 52-week, phase 3, open-label trial. All patients received CTN SR BID, titrated to 400 mg/d by day 8, and fixed thereafter. Long-term safety was assessed primarily by treatment emergent adverse events (TEAEs); clinical laboratories, ECGs, Study Medication Withdrawal Questionnaire (SMWQ), and Columbia-Suicide Severity Rating Scale (C-SSRS) were also assessed. Exploratory efficacy was evaluated with AISRS, Clinical Global Impression-Severity of Illness Scale (CGI-S), and ADHD Impact Module-Adult (AIM-A). Baseline was relative to the first open-label CTN dose administered. Results: Of 662 patients enrolled, 345 completed the trial. 401 (61.4%) experienced TEAEs, most commonly insomnia (8.0%), nausea (7.7%) diarrhea and headache (7% each). Serious AEs occurred in 12 (1.8%) patients; none were considered CTN-related. SMWQ scores were low throughout. C-SSRS defined suicidal ideation/behavior occurred in 13 (2.0%) patients. Exploratory efficacy improved across all assessments. Conclusions: Open-label trial results demonstrate that CTN SR 400 mg is a safe and effective long-term treatment for ADHD in adults.