Impact of Centanafadine on the ASRS After 6 Weeks of Treatment of ADHD in Adults: A Pooled Analysis of Two Phase 3 Trials

Hypothesis/Objective: To evaluate the impact of centanafadine (CTN)—a norepinephrine, dopamine, serotonin reuptake inhibitor—on patient-reported assessment of the frequency of core symptoms of ADHD after 6 weeks of treatment in adults (18-55y).

Methods: Data from two identically designed phase 3 trials were pooled. Patients 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) total, as well as the Inattentive (IA) and Hyperactive/Impulsive (H/I) subscale scores at Week 6. Results of ASRS patient-reported assessment complement the findings of the clinician-based assessment of the AISRS. Endpoints were analyzed using a mixed-effects model for repeated measure without adjusting for multiplicity and are therefore descriptive.

Results: At Week 6, adults treated with CTN reported numerically greater improvements in ADHD symptom frequency per ASRS total score vs placebo (least-squares mean difference 200mg: −4.82, P < 0.0001; 400mg: −5.29; P < 0.0001). Week 6 ASRS effect sizes were 0.36 for CTN 200mg and 0.39 for 400mg, comparable with the effect sizes of AISRS (CTN 200mg: 0.33 and 400mg: 0.34). Additionally, CTN demonstrated similar numerically greater 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=0.0007; 400mg: −2.5, P < 0.0001) subscale scores, improving the frequency of core ADHD symptoms vs placebo at Week 6.

Conclusions: Results of this pooled analysis indicate that the subjective experiences of adult patients with ADHD corresponded with the clinician-rated improvements of core ADHD symptoms after treatment with CTN.