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

Abstract

Background: Centanafadine (CTN) is a potential first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) currently in development for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults. Safety, tolerability, and exploratory efficacy of CTN sustained release (SR) in adults were assessed over 52 weeks.

Methods: Adults were enrolled after completing a phase 3 pivotal trial or de novo. The monitoring schedule employed a screening (up to 28 d for de novo group only), 52-week open-label, and 10-day safety follow-up periods. Participants received CTN SR 400 mg total daily dose, twice daily. Safety assessments included treatment-emergent adverse events (TEAEs), clinical laboratories, vital signs, electrocardiogram measures, the Study Medication Withdrawal Questionnaire, and the Columbia-Suicide Severity Rating Scale. Exploratory efficacy was assessed using the Adult Investigator Symptom Rating Scale (AISRS) and the Clinical Global Impression of Severity (CGI-S). Safety was analyzed with a mixed-effect model; efficacy was reported using summary statistics.

Results: Of 662 adults enrolled [mean (SD) age, 36.7 (10.1) y; 51.1% female; 82.9% white], 653 received CTN SR, and 345 completed the trial. Altogether, 61.4% reported ≥1 TEAE, mostly mild or moderate in severity; insomnia (8.0%), nausea (7.7%), diarrhea and headache (7.0% each) were most common. Eighty (12.3%) discontinued because of TEAEs. Serious adverse events occurred in 12 (1.8%) participants; none were CTN SR-related per investigators. AISRS total scores improved up to 57% and CGI-S by 1.5 points from baseline.

Conclusions: Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD.