Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) being investigated for the treatment of attention-deficit/hyperactivity disorder (ADHD). In a phase 2a study in adult males with ADHD, CTN sustained release (CTN SR) treatment significantly improved ADHD Rating Scale-IV (ADHD-RS-IV) total and subscale scores and was well tolerated. Additional efficacy outcomes from this study are reported.

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, 4th Edition criteria for ADHD and had a baseline ADHD-RS-IV total score ≥28 and Clinical Global Impression-Severity score of ≥4. The study had a screening period, a 1-week placebo run-in, and a 4-week CTN SR treatment phase. Previously unreported secondary outcomes of ADHD-RS-IV change from end of the single-blind placebo run-in and ADHD-RS-IV response (≥30% and ≥50% score reductions) at weeks 1, 2, 3 (on-treatment), and 6 (follow-up) are presented. Analyses were based on observed results using descriptive statistics.

Of 45 patients enrolled, 41 received ≥1 dose of study medication and 37 completed the 4-week treatment phase (mean [SD] age, 38.24 [11.88] years; 91.9% White). At baseline, mean (SD) ADHD-RS-IV total, Inattentive subscale, and Hyperactive/Impulsive subscale scores were 38.7 (6.19), 22.81 (2.55), and 15.89 (4.8), respectively. Mean (SD) changes 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. Correspondingly, mean (SD) changes in Inattentive subscale scores were −6.32 (4.99), −9.76 (6.4), and −12.16 (6.61) at weeks 1, 2, and 3, and −6.36 (5.7) at week 6, and in Hyperactive/Impulsive subscale scores were −4.81 (4.74), −6.38 (5.94), and −8.7 (5.81) at weeks 1, 2, and 3, and −5.17 (4.33) at week 6. ADHD-RS-IV ≥30% response was observed in 13 (35.14%), 23 (62.16%), and 28 (75.68%) patients at weeks 1, 2, and 3, and in 12 (33.33%) patients at week 6. ADHD-RS-IV ≥50% response was observed in 6 (16.22%), 16 (43.24%), and 23 (62.16%) patients at weeks 1, 2, and 3, and in 8 (22.22%) patients at week 6. The pattern of ≥30% and ≥50% response in Inattentive and Hyperactive/Impulsive subscale scores was similar to that observed with ADHD-RS-IV total score response.

These secondary outcomes support published primary results showing that CTN SR improved ADHD-RS-IV total and subscale scores. CTN SR treatment improved total ADHD symptoms within the first 2 weeks and was well tolerated. These findings support the usefulness of CTN SR, a potential first-in-class NDSRI, in providing rapid treatment benefit to adults with ADHD.

Study Registration: NCT01939353

Previous presentation: ASCP 2023, May 30–June 2, 2023, Miami Beach, FL

Otsuka