• The first trial (NCT05257265) was a pivotal Phase 3, randomized, double-blind, three-arm, fixed-dose trial to evaluate the efficacy, safety, and tolerability of centanafadine for adolescents with ADHD from the ages of 13 to 17 years.
• The second trial (NCT05428033) was a pivotal Phase 3, randomized, double-blind, 3-arm, fixed-dose trial to evaluate the efficacy, safety, and tolerability of centanafadine for children with ADHD from the ages of 6 to 12 years

The trials were similar in design; both were three-arm, double-blind, fixed-dose trials in which patients were randomized to receive either low-dose centanafadine, high-dose centanafadine, or placebo.

"Otsuka is committed to finding novel solutions for complex, underserved medical needs," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "We are pleased these pivotal Phase 3 results demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD, a condition that can affect every aspect of life."

Topline Results

The primary outcome in both trials was the change from baseline to week 6 in the ADHD Rating Scale (ADHD-RS-5) symptoms total score.

The first trial (NCT05257265) in adolescents aged 13-17 met its primary endpoint by demonstrating improvements from baseline on the ADHD-RS-5 scale. Patients receiving centanafadine saw statistically significant improvements compared to placebo for both the average effect of the high and low dose ([p=0.0099]) and for the high dose ([p=0.0006]) centanafadine-treated group. The low dose centanafadine-treated did not reach statistical significance.

The second trial (NCT05428033) in children aged 6-12 met its primary endpoint by demonstrating improvements from baseline on the ADHD-RS-5 scale. Patients receiving centanafadine saw statistically significant improvements compared to placebo for both the average effect of the high and low dose ([p=0.0039]) and for the high dose ([p=0.0008]) centanafadine-treated group. The low dose centanafadine-treated did not reach statistical significance.

In both trials, the high dose centanafadine showed separation from placebo as early as week 1, the first post-baseline timepoint, with the effect maintained throughout the study period.

In a pooled analysis across the two studies, the most frequently observed side effects for centanafadine (>2 percent and more frequent than placebo) included decreased appetite, nausea, rash, fatigue, upper abdominal pain and somnolence. Overall, the safety and tolerability results were consistent with the profile of centanafadine seen within the wider clinical development program.

Full study results are not yet available. The trial results are planned to be submitted for scientific publication at a later date. Clinical pharmacology studies and long-term stability studies are underway, and the NDA will be filed in the U.S. as soon as these are completed.