Centanafadine Sustained Release in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder: Secondary Outcomes From a Phase 2a Study

This trial was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Introduction: Centanafadine (CTN) is a norepinephrine/dopamine/serotonin reuptake inhibitor being investigated for treatment of attention-deficit/hyperactivity disorder (ADHD). In a phase 2a study in adult males with ADHD (NCT01939353), 4 weeks of sustained-release CTN (CTN SR) treatment significantly improved ADHD Rating Scale-IV (ADHD-RS-IV) scores. Additional efficacy outcomes from this study are reported here. Methods: This flexible-dose (CTN SR 200–500 mg/d), single-blind, exploratory study enrolled males aged 18–55 years who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD. Secondary outcomes included ADHD-RS-IV (total and subscale) score changes from baseline and response (≥30% and ≥50% reductions) at weeks 1, 2, 3 (on-treatment), and 6 (follow-up). Results: Of 45 patients enrolled, 41 received ≥1 dose of CTN SR and 37 completed the 4-week treatment phase (Mean±SD age, 38.24±11.88 years; 91.9% White). Mean±SD decreases (improvement) in ADHD-RS-IV total scores were −11.14±8.64, −16.14±11.08, and −20.86±11.11 at weeks 1, 2, and 3 and −11.53±8.78 at week 6. ADHD-RS-IV ≥30% response was observed in 35.14%, 62.16%, and 75.68% of patients at weeks 1, 2, and 3 and in 33.33% at week 6. ADHD-RS-IV ≥50% response was observed in 16.22%, 43.24%, 62.16% of patients at weeks 1, 2, and 3 and in 22.22% at week 6. ADHD-RS-IV subscale score results were consistent with ADHD-RS-IV total scores. CTN-SR was well-tolerated. Conclusion: These findings show that CTN SR improved in ADHD-RS-IV scores within the first 2 weeks of treatment and support the usefulness of CTN SR in providing rapid benefit for adults with ADHD.