Phase III trials show efficacy of EB 1020 in attention-deficit hyperactivity disorder.- Otsuka Pharmaceutical

Otsuka Pharmaceutical has announced positive top-line results from two, six-week, phase III clinical trials that evaluated the efficacy, safety and tolerability of oral EB 1020 (centanafadine), a novel investigational compound for the treatment of adult patients with attention-deficit hyperactivity disorder (ADHD). In both trials, 200 mg and 400 mg total, daily oral doses of centanafadine demonstrated statistically significant improvement vs. placebo on the primary efficacy endpoint, change from baseline to Day 42 on the adult ADHD investigator symptom rating scale (AISRS) total score (p < 0.05 in the first study and p < 0.01 in the second study). AISRS is an interview-based evaluation of ADHD symptoms in adult patients, with hyperactive/impulsive and inattention subscales. In both trials, statistically significant improvements versus placebo were also observed in the key secondary efficacy outcome, CGI-S (Clinical Global Impression – Severity scale) change from baseline to Day 42 (p < 0.05). In a pooled-analysis across the two studies, the most frequently observed side effects for centanafadine (>5 percent and more frequent than placebo) included decreased appetite, headache, nausea, dry mouth, upper respiratory tract infection and diarrhea; no side effect was observed in greater than 7 percent of patients. The company also plans to investigate the effects of centanafadine in pediatric patients with ADHD, as well as to discuss next steps with the U.S. Food and Drug Administration. Comment: Centanafadine is a serotonin-norepinephrine-dopamine, triple-reuptake inhibitor. Approximately, 900 adult patients from age 18 to 55 years old, and diagnosed with ADHD, were randomized in the two phase III studies. The studies were randomized, double-blind, multicenter, and placebo-controlled with parallel groups. Patients were randomized 1:1:1 to receive either centanafadine doses of 100 or 200 mg, twice daily (total daily dose of 200 mg or 400 mg, respectively), or placebo twice daily. A long-term safety and tolerability study of centanafadine in a 400 mg total daily dose is ongoing, with top-line results expected in 2021.