Centanafadine for Treatment of ADHD in Children, Adolescents, and Adults Accepted By FDA for Priority Review

The FDA accepted for priority review the new drug application (NDA) for centanafadine (Otsuka Pharmaceutical) for the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. According to the manufacturer’s news release, the Prescription Drug User Fee Act (PDUFA) target action date is set for July 24, 2026.¹

Centanafadine is an investigational first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). It is only administered orally once per day and comes as an extended-release capsule. The NDA was supported by findings from 4 pivotal phase 3 clinical trials that evaluated centanafadine’s safety and efficacy across patient populations.¹

“ADHD manifests differently across patients, highlighting the importance of having multiple therapeutic approaches available,” John Kraus, MD, PhD, executive vice president and chief medical officer of Otsuka Pharmaceutical Development & Commercialization, Inc, said in a news release. “The FDA’s acceptance and priority review designation of our NDA for centanafadine marks an important milestone in our effort to bring forward a novel treatment option for people living with ADHD.”¹

Clinical Data Supporting the FDA’s Action

The 4 multicenter, randomized, double-blind, placebo-controlled clinical trials enrolled children (NCT05428033)², adolescents (NCT05257265)³, and adults (NCT03605680 and NCT03605836)^4,5 with ADHD to assess the safety and efficacy of centanafadine. In these respective trials, patients with ADHD were randomly assigned to receive the following: low-dose (n = 154) or high-dose (n = 162) centanafadine or placebo (n = 164) once daily for 6 weeks⁶; 164.4 mg (n = 155) or 328.8 mg (n = 155) of centanafadine or placebo (n = 149)⁷; and 200 mg (n = 149, n = 145) or 400 mg (n = 149, n = 143) of centanafadine or placebo (n = 148, n = 142) once per day.⁸

The primary end points were the change from baseline in the ADHD Rating Scale version 5 (ADHD-RS-5) symptoms total raw score at week 6 for the child and adolescent studies and the change from baseline at day 42 in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score for the adult studies. For the adult studies, the secondary end point was change from baseline in the Clinical Global Impression–Severity of Illness Scale.⁸

Child Study

Results indicated that, at week 6, improvements in ADHD-RS-5 symptoms total raw score were significantly greater in patients treated with high-dose centanafadine than with placebo (–16.3 vs –10.8; P < .001). Additionally, high-dose centanafadine showed separation from placebo as early as week 1, the first postbaseline time point, with the effect maintained throughout the study period. Low-dose centanafadine did not show statistical significance in the primary end point, reported the authors.⁷

Additionally, treatment-emergent adverse events (TEAEs) occurred in 52 (35%), 61 (39%), and 39 (25%) of patients in the low-dose, high-dose, and placebo groups, respectively. The most common TEAEs were decreased appetite (n = 23; 5%), rash (n = 14; 3%), and vomiting (n = 13; 3%), and were observed in all treatment groups. TEAEs were observed to be of mild or moderate severity.⁶

Adolescent Study

At week 6, improvements in ADHD-RS-5 symptoms’ total raw score were significantly greater with the higher dose of centanafadine than with placebo (–18.50 vs –14.15; p = .0006). The lower dose of centanafadine did not meet the primary end point. Additionally, the high dose of centanafadine demonstrated separation from placebo at week 1, the first postbaseline timepoint, with the effect maintained throughout the study.⁷

TEAEs occurred in 48 (31.4%), 76 (50.3%), and 35 (23.8%) patients in the low-dose, high-dose, and placebo groups, respectively. The most common (≥5% in any group) TEAEs were decreased appetite, nausea, headache, and rash, of which most were mild or moderate in severity. Only 3 events were severe: liver function test increase (n = 1); aggression (n = 1), of which both were in the low-dose group; and somnolence (n = 1) in the placebo group.⁷

Adult Studies

At day 42, statistically significant mean differences in AISRS total score were observed in favor of centanafadine versus placebo in study 1 (200 mg: −3.16, P = .019; 400 mg: −2.74, P = .039) and study 2 (200 mg: −4.01, P = .002; 400 mg: −4.47, P = .001). Additionally, effect sizes compared with placebo in study 1 were −0.28 and −0.24 for 200 mg and 400 mg, respectively, and in study 2 were −0.37 and −0.40 for 200 mg and 400 mg, respectively.⁸

The overall rate of TEAEs was low, wrote the authors, but there was a small increase in TEAE occurrence with increasing dose. Incidences of serious TEAEs and abuse-potential-related AEs were low.⁸

“If approved, centanafadine would offer a first-in-class NDSRI option designed to support broad symptom management. We extend our sincere gratitude to the patients, caregivers, and investigators whose participation made this milestone possible,” Kraus said in the news release.¹

REFERENCES

1. Otsuka Pharmaceutical. Otsuka Announces FDA Acceptance and Priority Review of New Drug Application for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults. News release. January 27, 2026. Accessed January 29, 2026. https://www.otsuka-us.com/news/otsuka-announces-fda-acceptance-and-priority-review-new-drug-application-centanafadine

2. A Trial of Centanafadine Efficacy and Safety in Children With Attention-deficit/​ Hyperactivity Disorder (ADHD). ClinicalTrials.gov identifier: NCT05428033. Updated July 22, 2025. Accessed January 29, 2026. https://clinicaltrials.gov/study/NCT05428033

3. A Trial of Centanafadine Efficacy and Safety in Adolescents With Attention- Deficit/​Hyperactivity Disorder. ClinicalTrials.gov identifier: NCT05257265. Updated September 27, 2024. Accessed January 29, 2026. https://clinicaltrials.gov/study/NCT05257265

4. A Trial Evaluating the Efficacy, Safety, & Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/​Hyperactivity Disorder. ClinicalTrials.gov identifier: NCT03605680. Updated March 15, 2022. Accessed January 29, 2026. https://clinicaltrials.gov/study/NCT03605680

5. A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/​Hyperactivity Disorder. ClinicalTrials.gov identifier: NCT03605836. Updated October 18, 2021. Accessed January 29, 2026. https://clinicaltrials.gov/study/NCT03605836

6. Caroline L. Ward, Timothy E. Wilens, Na Jin, Osman Turkoglu, Taisa Skubiak, Ann C. Childress; 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

7. 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. 2025. doi:10.1016/j.jaac.2025.06.023

8. Alder 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