TRIAL SUCCESS

Otsuka's centanafadine beats placebo on ADHD and anxiety in Phase 3b trial

The 315-patient study hit its primary endpoint in adults with ADHD and comorbid anxiety, adding a second symptom domain to the drug's evidence base weeks before its FDA decision.

By AppliedXLJune 25, 2026Trial NCT06973577

Executive Summary

A Phase 3b trial of Otsuka's centanafadine met its primary endpoint in adults with ADHD and comorbid anxiety, with the drug separating from placebo on the core ADHD symptom scale.
The result lands weeks ahead of the FDA's decision on centanafadine's broader ADHD application, adding a comorbid-anxiety data point to the drug's evidence base without changing what that decision itself will turn on.
A secondary anxiety measure also separated from placebo, indicating the drug's effect was not confined to ADHD symptoms alone in this dually diagnosed population.
Centanafadine's mechanism, blocking reuptake of dopamine, norepinephrine and serotonin together, has direct peers among approved ADHD stimulants and nonstimulants, so the readout's value lies in extending an established profile into a harder-to-treat comorbid population rather than opening new mechanistic ground.

The result

Otsuka Pharmaceutical Development & Commercialization and Otsuka Pharmaceutical Co. announced on June 25, 2026 that centanafadine XR 280 mg once daily met the primary endpoint of a Phase 3b trial (NCT06973577) in adults with ADHD and comorbid generalized anxiety disorder and/or social anxiety disorder. Patients on centanafadine improved by an LS mean of -18.5 points on the Adult Investigator Symptom Rating Scale (AISRS) total score, versus -12.6 for placebo, a treatment difference of -5.87 points with p<0.0001. The company said statistical separation from placebo was visible as early as week 1 and held through the 8-week trial. NCT06973577+1

Probability of Success

Endpoint Met33%

Completes94%

Clinical Significance29%

Regulatory57%

The design

The randomized, double-blind, placebo-controlled trial enrolled 315 adults aged 18 to 65, all with a confirmed ADHD diagnosis and a comorbid diagnosis of generalized anxiety disorder or social anxiety disorder, screened using the Mini-International Neuropsychiatric Interview. Patients required a baseline AISRS score of at least 28 and a Hamilton Anxiety Rating Scale (HAM-A) score of at least 20 to enroll. The primary endpoint was change in AISRS total score from baseline versus placebo at week 8; the key secondary endpoint was change in HAM-A total score over the same period. On that secondary measure, centanafadine also separated from placebo, with an LS mean change of -12.5 versus -10.6, a difference of -1.92 points (p=0.02). NCT06973577+1

Safety

The most frequent side effects with centanafadine, each occurring in more than 5% of patients and more often than with placebo, were nausea, decreased appetite, diarrhea, insomnia, dry mouth and vomiting. Otsuka said the safety and tolerability profile was consistent with centanafadine's known profile and with what would be expected in a population carrying both ADHD and anxiety diagnoses. Otsuka

The regulatory backdrop

Centanafadine is under FDA review for ADHD in children, adolescents and adults, with Priority Review granted and a PDUFA target action date of July 24, 2026. This Phase 3b trial in comorbid anxiety was not the pivotal study behind that pending application; it supplements the evidence base for centanafadine's effect on core ADHD symptoms in a population where anxiety commonly complicates presentation and treatment. Full results are expected to be presented at a scientific meeting rather than through the trial's ClinicalTrials.gov results record, which had not yet posted data as of this readout. Otsuka+1

Where it sits competitively

Centanafadine acts on the dopamine, norepinephrine and serotonin transporters, and several direct comparators share the dopamine-transporter mechanism in ADHD, including Supernus Pharmaceuticals' viloxazine and Aytu BioPharma's amphetamine, both already in Phase 4 testing in the same indication. Centanafadine itself carries two other Phase 3 programs in ADHD, run by Otsuka Pharmaceutical Co., underscoring that this readout adds a comorbid-anxiety data point onto an already advancing registrational package rather than opening a new therapeutic hypothesis. NCT06973577

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.