Centanafadine hits primary and key secondary endpoints in ADHD phase 3b trial

A phase 3b study of Otsuka’s centanafadine has met its primary endpoint in adults with attention-deficit/hyperactivity disorder (ADHD) and comorbid anxiety. The drug is currently under Priority Review by the FDA for the treatment of ADHD in children, adolescents and adults, with a Prescription Drug User Fee Act target action date of July 24, 2026.

The announcement was made via a company news release on June 25.

Centanafadine is an investigational, first-in-class norepinephrine, dopamine and serotonin reuptake inhibitor (NDSRI). The FDA initially accepted Otsuka’s New Drug Application in January 2026.

Trial design

The study enrolled 315 adults ages 18 to 65 with ADHD and comorbid generalized anxiety disorder and/or social anxiety disorder. Patients received either centanafadine XR 280 mg once daily or placebo.

Efficacy results

Results show that centanafadine demonstrated statistically significant and clinically relevant improvement on the Adult Investigator Symptom Rating Scale total score compared to placebo at week 8. The least squares mean change was -18.5 for centanafadine versus -12.6 for placebo, a treatment difference of -5.87.

The study also showed statistically significant improvement on a key secondary endpoint, the Hamilton Anxiety Rating Scale (HAM-A) total score, at week 8. The average change was -12.5 for centanafadine compared with -10.6 for placebo, a treatment difference of -1.92.

Full results from the study will be presented at an upcoming scientific meeting, the release states.

“Adults with ADHD and comorbid anxiety represent a substantial and particularly challenging population to treat,” John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka, said in the 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.”

Safety

Side effects occurred in at least 5% of patients, the most common being nausea, decreased appetite, diarrhea, insomnia, dry mouth and vomiting. The data collected so far also suggest the drug has low potential for abuse. The safety and tolerability profile observed in the study was consistent with centanafadine's established safety profile in an ADHD and comorbid anxiety population, according to the release.

About ADHD and anxiety

ADHD is a chronic neurodevelopmental disorder that causes impairments in attention, hyperactivity and impulsivity. In the United States, it affects approximately 7 million children and 15.5 million adults, according to the Centers for Disease Control and Prevention. As many as half of all ADHD patients also suffer from at least one comorbid anxiety disorder, which has been associated with higher rates of suicidality and hospitalization. Individuals with ADHD and comorbid anxiety disorder are also more likely to have worse clinical presentations, achieve lower occupational outcomes and experience a reduced quality of life.