EXECUTIVE FUNCTION SYMPTOM OUTCOMES IN ADULTS WITH ADHD TREATED WITH CENTANAFADINE: A POOLED POST HOC ANALYSIS OF TWO PHASE 3 TRIALS

Background

Attention-deficit/hyperactivity disorder (ADHD) in adults frequently includes impairments in executive functions such as organization, planning, time management, and working memory. This pooled post hoc analysis of two phase 3 trials evaluated the effect of centanafadine (CTN)—a norepinephrine, dopamine, serotonin reuptake inhibitor—on patient-reported assessment of executive functioning using the adult ADHD Self-Report Scale (ASRS) Expanded Version after 6 weeks of treatment in adults with ADHD.

Methods

Data from two identically designed phase 3 trials were pooled. Eligible patients (aged 18–55 years) with a primary ADHD diagnosis per DSM-5 were randomized to receive CTN 200 or 400mg/day or placebo. Exploratory endpoints included changes from baseline in the Executive Function (EF) subscale score and individual EF line items from the ASRS Expanded Version at Week 6. The ASRS Expanded Version is a validated, self-administered questionnaire that includes 9 items assessing aspects of executive dysfunction, with responses rated on a 5-point Likert scale (0=never to 4=very often). Endpoints were analyzed using a mixed-effects model for repeated measure without adjusting for multiplicity.

Results

A total of 744 adults were included in the efficacy sample (CTN 200mg, n=242; 400mg, n=241; placebo, n=261). At Week 6, adults treated with CTN reported improvements from baseline in the ASRS EF subscale compared with placebo, reflecting reductions in the frequency of patient-reported executive functioning difficulties (200mg: −2.4, P < 0.0001; 400mg: −2.6, P < 0.0001). Effect sizes (Cohen’s D) for the ASRS EF subscale were 0.36 for CTN 200mg and 0.38 for 400mg, and were comparable in magnitude to those for core symptom subscales assessing Inattention and Hyperactivity/Impulsivity. Consistent with the subscale-level findings, improvements from baseline vs placebo were observed across individual ASRS EF line items at Week 6, including those related to time management, planning and prioritization, task initiation and completion, and working memory–related difficulties.

Conclusions

In this pooled post hoc analysis, CTN was associated with improvements in patient-reported executive functioning in adults with ADHD, as assessed by the ASRS Expanded Version. Improvements were observed across a broad range of executive function items, including time management, planning and prioritization, task initiation and completion, and working memory–related difficulties.