Centanafadine XR improved adult ADHD symptoms in a phase 3b trial of patients with comorbid generalized or social anxiety disorder.
Otsuka reported positive topline results from a randomized phase 3b trial of
“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 at Otsuka, said in the announcement. “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
Key Facts
The phase 3b study, registered as NCT06973577, enrolled 315 adults aged 18 to 65 years with ADHD and comorbid generalized anxiety disorder and/or social anxiety disorder. The trial was randomized, double-blind, and placebo-controlled, evaluating centanafadine XR 280 mg once daily vs placebo over 8 weeks.¹
The primary endpoint was change from baseline in Adult Investigator Symptom Rating Scale (AISRS) total score at week 8. According to Otsuka, patients assigned to centanafadine had a least-squares mean change of –18.5 compared with –12.6 for placebo, corresponding to a treatment difference of –5.87 points (P < .0001). The company reported statistical separation from placebo as early as week 1, the first postbaseline assessment, with separation maintained through week 8.¹
Centanafadine also met a key secondary endpoint assessing anxiety symptoms. Change from baseline in Hamilton Anxiety Rating Scale total score at week 8 was –12.5 with centanafadine vs –10.6 with placebo, for a treatment difference of –1.92 points (P = .02). Otsuka stated that other secondary endpoints assessing ADHD-associated features supported the primary efficacy findings, although detailed data were not included in the topline announcement.¹
The most frequently reported adverse events occurring in more than 5% of centanafadine-treated participants and more often than placebo were nausea, decreased appetite, diarrhea, insomnia, dry mouth, and vomiting. The company characterized the safety and tolerability profile as consistent with prior experience with centanafadine and with an ADHD population with comorbid anxiety.¹
ADHD is a chronic neurodevelopmental disorder characterized by developmentally inappropriate patterns of inattention and/or hyperactivity-impulsivity that interfere with functioning.² In the US, recent CDC data have estimated ADHD diagnoses in approximately 7 million children and 15.5 million adults, underscoring the relevance of adult ADHD as a clinical and public health issue.³ Anxiety disorders are among the most common psychiatric comorbidities in adults with ADHD and may complicate diagnosis, symptom attribution, functional impairment, and treatment selection.⁴
Centanafadine is an investigational norepinephrine, dopamine, and serotonin reuptake inhibitor. Unlike stimulant medications, which remain widely used for ADHD, centanafadine is being developed as a nonstimulant option; however, it has not yet received FDA approval. Otsuka stated the drug is currently
For clinicians, the phase 3b findings are notable because adults with ADHD and co-occurring anxiety are commonly encountered in practice, yet trial data specifically focused on this subgroup are limited. The reported improvement on both ADHD and anxiety scales may be clinically relevant, but interpretation is constrained by the topline nature of the release. Full assessment will require peer-reviewed or congress-presented data, including baseline severity, discontinuation rates, adverse event rates by arm, rescue medication policies, multiplicity control for secondary outcomes, and subgroup analyses by anxiety diagnosis.
The next regulatory milestone is the FDA action date for centanafadine’s broader ADHD application. Otsuka said full phase 3b results will be presented at an upcoming scientific meeting. Until regulatory review is complete, centanafadine remains investigational in the US.¹
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