ASRS OUTCOMES ACROSS CORE AND EXPANDED SYMPTOM DOMAINS AFTER 6 WEEKS OF CENTANAFADINE TREATMENT IN ADULTS WITH ADHD: A POOLED POST HOC ANALYSIS OF TWO PHASE 3 TRIALS

Background

Attention-deficit/hyperactivity disorder (ADHD) is a chronic and prevalent neurodevelopmental disorder in adults, characterized by core symptoms of inattention, hyperactivity, and impulsivity . Despite treatments that manage core symptoms, significant unmet needs persist for adults with ADHD, particularly with respect to associated features such as emotional dysregulation and executive dysfunction . 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 the frequency of core symptoms and associated features of ADHD after 6 weeks of treatment in adults aged 18–55 years.

Methods

Data from two identically designed phase 3 trials were pooled . Eligible patients 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 adult ADHD Self-Report Scale (ASRS-18) Total score and Inattention (IA) and Hyperactive/Impulsive (H/I) subscale scores, as well as Executive Function (EF) and Emotional Dyscontrol (ED) subscale scores from the ASRS Expanded Version at Week 6. The ASRS is a validated, self-administered questionnaire used to screen, assess, and quantify symptom severity using 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 greater improvements in ADHD symptom frequency per ASRS Total score vs placebo (least-squares mean difference 200mg: −4.8, P < 0.0001; 400mg: −5.3; P < 0.0001 ). CTN demonstrated similar patient-reported improvements in the ASRS IA (200mg: −2.9, P < 0.0001; 400mg: −2.8, P < 0.0001) and H/I (200mg: −2.0, P < 0.0001; 400mg: −2.6, P < 0.0001) subscale scores vs placebo at Week 6 . Effect sizes (Cohen’s D) were 0.42 and 0.45 for ASRS IA and 0.30 and 0.42 for H/I at the 200mg and 400mg doses, respectively. Consistent with the core symptom domains, improvements were observed in both the EF (200mg: −2.4, P=0.0007; 400mg: −2.5, P < 0.0001) and the ED (200mg: −0.9, P=0.0023; 400mg: −0.9, P < 0.0006) subscale scores of the ASRS Expanded Version. For ASRS EF, effect sizes were 0.36 at 200mg and 0.38 at 400mg; for ED, corresponding effect sizes were 0.27 and 0.31, respectively.

Conclusions

CTN was associated with improvements from baseline in the ASRS Total score and subscales assessing both core symptoms and associated features of ADHD, including executive dysfunction and emotional dysregulation, with effects of similar magnitude across domains.