Otsuka reported positive Phase 3b results for centanafadine XR in adults with ADHD and comorbid anxiety, meeting primary and secondary endpoints. The investigational first-in-class triple reuptake inhibitor is under FDA Priority Review, with a PDUFA date of July 24, 2026
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Otsuka have reported positive topline results from the Phase 3b study (NCT06973577) evaluating once-daily centanafadine XR 280 mg in adults with attention-deficit/hyperactivity disorder (ADHD) and comorbid anxiety.
The trial met its primary and key secondary endpoints, demonstrating statistically significant improvements in both ADHD and anxiety symptoms compared with placebo. The data further support centanafadine as it undergoes FDA Priority Review for the treatment of ADHD in children, adolescents, and adults.
First-in-Class Triple Reuptake Inhibitor for ADHD
Centanafadine is an investigational first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). Unlike conventional stimulant therapies that primarily target dopamine and norepinephrine, centanafadine also inhibits serotonin reuptake, offering a distinct pharmacological approach to treating ADHD.
ADHD is a chronic neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity. Anxiety disorders frequently coexist with ADHD, affecting up to half of adults with the condition. Patients with both disorders often experience greater functional impairment, poorer quality of life, and more complex treatment challenges than those with ADHD alone.
Phase 3b Trial Demonstrated Early and Sustained Clinical Benefit
The randomized, double-blind, placebo-controlled Phase 3b study enrolled 315 adults aged 18 to 65 years with ADHD and either generalized anxiety disorder (GAD) or social anxiety disorder (SAD).
The primary endpoint evaluated change from baseline in the Adult Investigator Symptom Rating Scale (AISRS) total score after eight weeks of treatment. Patients receiving centanafadine achieved significantly greater improvement than those receiving placebo, with a least-squares mean change of -18.5 versus -12.6, corresponding to a treatment difference of -5.87 points (p<0.0001). Clinical separation from placebo emerged as early as Week 1 and remained consistent throughout the study.
The trial also met its key secondary endpoint. Centanafadine significantly improved anxiety symptoms measured by the Hamilton Anxiety Rating Scale (HAM-A), producing a least-squares mean change of -12.5 compared with -10.6 for placebo, with a treatment difference of -1.92 points (p=0.02). Additional secondary endpoints evaluating ADHD-associated features also favored centanafadine, further supporting its overall clinical benefit.
The most commonly reported adverse events occurring in more than 5% of patients and more frequently than placebo were nausea, decreased appetite, diarrhea, insomnia, dry mouth, and vomiting. Investigators reported that the overall safety and tolerability profile remained consistent with previous centanafadine studies.
Expanding Evidence in a Difficult-to-Treat Population
Commenting on the findings, John Kraus, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Otsuka, said adults living with both ADHD and anxiety represent one of the most challenging patient populations to manage. He noted that the new data broaden the evidence supporting centanafadine’s potential across diverse adult ADHD presentations while reinforcing its clinical profile.
FDA Decision Expected Next Month
Centanafadine is currently under FDA Priority Review for the treatment of ADHD in children, adolescents, and adults, with a Prescription Drug User Fee Act (PDUFA) target action date of July 24, 2026. Otsuka plans to present the complete Phase 3b results at an upcoming scientific meeting.
If approved, centanafadine could become the first NDSRI available for ADHD treatment, providing a potential non-stimulant therapeutic option for patients, particularly those with coexisting anxiety disorders where treatment selection remains challenging.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.