First-in-Class Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitor for ADHD

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Otsuka Pharmaceuticals announced positive results from 2 phase 3 clinical trials that evaluated the efficacy, safety, and tolerability of centanafadine—a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor for the treatment of adolescents and children with attention-deficit/hyperactivity disorder (ADHD).¹

“Otsuka is committed to finding novel solutions for complex, underserved medical needs,” said John Kraus, MD, PhD, executive vice president and chief medical officer of Otsuka Pharmaceutical Development & Commercialization. “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.”

The first trial (NCT05257265) evaluated the efficacy, safety, and tolerability of centanafadine for adolescents aged 13 to 17 years with ADHD, while the second trial (NCT05428033) evaluated centanafadine for children aged 6 to 12 years with ADHD.The primary endpoint of both trials was change from baseline to week 6 in the ADHD Rating Scale (ADHD-RS-5) symptoms total score, and both trials met it. Both trials were 6-week, 3-arm, double-blind, fixed-dose trials in which participants were randomized to receive low-dose centanafadine, high-dose centanafadine, or placebo; dose was determined by body weight.

In the first trial, participants receiving centanafadine saw statistically significant improvements compared with 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 groups. In the second trial, participants receiving centanafadine saw statistically significant improvements compared with 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 groups in both trials did not reach statistical significance; however, the high dose centanafadine group showed improvement over placebo as quickly as week 1.

Across both studies, the most common adverse effects for centanafadine included decreased appetite, nausea, rash, fatigue, upper abdominal pain, and somnolence.

Reference

1. Otsuka Pharmaceutical announces positive topline results from two pivotal phase 3 trials of centanafadine as a treatment for adolescents and children with attention-deficit/hyperactivity disorder (ADHD). Otsuka. News release. October 27, 2023. https://otsuka-us.com/news/otsuka-pharmaceutical-announces-positive-topline-results-two-pivotal-phase-3-trials