Centanafadine Demonstrates Statistically Significant, Clinically Relevant Improvements in ADHD Symptoms

Researchers have announced positive topline results from a phase 3b clinical trial (NCT06973577) evaluating centanafadine XR (Otsuka Pharmaceutical) 280 mg once daily in adults with attention-deficit/hyperactivity disorder (ADHD) and comorbid anxiety. Full results will be presented at an upcoming scientific meeting.^1,2

What is Centanafadine?

Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) with a new drug application (NDA) for the treatment of ADHD in children, adolescents, and adults accepted for FDA priority review in January 2026. It was simultaneously granted a Prescription Drug User Fee Act (PDUFA) target action date of July 24, 2026.³

Clinical data supporting centanafadine’s NDA demonstrated that the treatment resulted in statistically significant improvements in core ADHD symptoms, with higher doses consistently meeting primary end points.^4-6 In adults aged 18 to 55 years, 2 phase 3 trials found that both 200 mg and 400 mg daily doses significantly reduced ADHD symptoms compared to placebo, as measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS). Significant improvements were observed as early as day 7 in 1 study, which were maintained through the 6-week treatment period. Key secondary end points, such as clinical global impressions of severity, also showed significant improvement.⁴

In adolescents aged 13 to 17 years, a 6-week trial found that a 328.8 mg dose met the primary end point, showing significantly greater improvements in the ADHD Rating Scale, version 5 (ADHD-RS-5) total score compared with placebo (p = .0006). This improvement was rapid, with separation from placebo observed at week 1 and maintained throughout the study, whereas the lower dose (164.4 mg) did not meet the primary end point.⁵

Similarly, in children aged 6 to 12 years, a weight-based high-dose regimen significantly improved ADHD-RS-5 scores compared to placebo (p < .001), with separation from the placebo also beginning at week 1. The low-dose regimen did not show a statistically significant difference from the placebo at the 6-week mark. Beyond improvements in core symptoms, studies in children and adolescents showed that treatment with a higher dose of centanafadine significantly improved executive functioning and inattention.⁶

Centanafadine Demonstrates Improvements in ADHD Symptoms

Findings from the current randomized, double-blind, placebo-controlled phase 3b clinical trial demonstrate that the primary end point was met. Centanafadine resulted in improvements from baseline on the AISRS total score compared with placebo at the 8-week point. Specifically, the 315 adult patients with ADHD and comorbid anxiety (generalized anxiety disorder and/or social anxiety disorder) treated with centanafadine demonstrated statistically significant and clinically relevant improvements compared to placebo [LS mean change, –18.5 vs –12.6; treatment difference, –5.87; p < .0001].¹

Statistical separation was seen as early as week 1, which was the first postbaseline timepoint and was maintained over the 8-week trial. Statistically significant improvements compared with placebo were also observed in the key secondary efficacy end point, which was change from baseline in Hamilton Anxiety Rating Scale total score at week 8 [LS mean change, –12.5 vs –10.6; treatment difference, –1.92; p = .02] and other secondary efficacy end points supporting the primary outcome results.¹

The most frequently observed adverse effects for centanafadine included nausea, decreased appetite, diarrhea, insomnia, dry mouth, and vomiting. The safety and tolerability profile was consistent with the known safety profile for centanafadine and an ADHD and anxiety comorbid population.¹

“Adults with ADHD and comorbid anxiety represent a substantial and particularly challenging population to treat,” John Kraus, MD, PhD, executive vice president and chief medical officer of Otsuka, said in a news release. “These results provide additional insight into centanafadine’s clinical profile and expand the evidence base supporting its potential in adults with ADHD across diverse patient presentations.”¹

REFERENCES

1. Otsuka Announces Positive Phase 3b Results for Centanafadine in Adults with ADHD and Comorbid Anxiety. Businesswire. News release. June 25, 2026. Accessed June 25, 2026. https://www.businesswire.com/news/home/20260625977962/en/Otsuka-Announces-Positive-Phase-3b-Results-for-Centanafadine-in-Adults-with-ADHD-and-Comorbid-Anxiety

2. P3b Short-term Study of CTN in Patients With ADHD and Comorbid Anxiety. ClinicalTrials.gov identifier: NCT06973577. Updated May 6, 2026. Accessed June 25, 2026. https://clinicaltrials.gov/study/NCT06973577

3. Otsuka Announces FDA Acceptance and Priority Review of New Drug Application for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults. Otsuka Pharmaceutical. News release. January 27, 2026. Accessed June 25, 2026. https://www.otsuka-us.com/news/otsuka-announces-fda-acceptance-and-priority-review-new-drug-application-centanafadine

4. Adler LA, Adams J, Madera-McDonough J, et al. Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. J Clin Psychopharmacol. 2022;42(5): 429-439. doi:10.1097/JCP.0000000000001575

5. Ward CL, Childress AC, Jin N, Turkoglu O, Skubiak T, Wilens TE. Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial. J Am Acad Child Adolesc Psychiatry. 2026;65(6):805-817. doi:10.1016/j.jaac.2025.06.023

6. Ward CL, Wilens TE, Jin N, Turkoglu O, Skubiak T, Childress AC. Efficacy and Safety of Centanafadine for ADHD Treatment in Children: A Randomized Clinical Trial. Pediatr Open Sci. 2025;1(3):1-11. doi:10.1542/pedsos.2024-000349