Centanafadine Hydrochloride

Pictured: Girl student having trouble concentrating/iStock, PeopleImages Otsuka Pharmaceutical on Friday posted top-line data from two Phase III studies, demonstrating that its attention deficit/hyperactivity disorder candidate centanafadine significantly improves symptoms in children and teenagers. Friday’s readouts come from attention deficit/hyperactivity disorder (ADHD) trials that are largely similar in design, employing three arms and fixed high or low doses of centanafadine which were given compared to placebo on a double-blinded basis. The main difference is in the study populations: one enrolled adolescent participants between the ages of 13 and 17 years, while the other included children aged six to 12 years. In the adolescent study, patients treated with high-dose centanafadine saw significantly better scores on the ADHD Rating Scale version 5 (ADHD-RS-5), a validated tool used to assess the severity of ADHD and the study’s primary endpoint. The average effect of both the high and low centanafadine doses was also significantly better than placebo. Centanafadine was similarly effective in children. ADHD-RS-5 scores significantly improved in patients who were treated with high-dose centanafadine, and the average treatment effect in both high-dose and low-dose groups was likewise statistically better than placebo. In the adolescent and pediatric trials, the benefits of high-dose centanafadine became apparent as early as the first post-baseline timepoint at week one, which was sustained for the rest of the study periods. However, both low-dose arms did not see significantly improved ADHD-RS-5 scores versus placebo. In terms of safety, pooling data from both studies demonstrated a tolerability pro was consistent with centanafadine’s broader clinical development program. The most common side effects included nausea, upper abdominal pain, somnolence and fatigue. While the full results from both studies are not yet available, these data “demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD,” John Kraus, chief medical officer of U.S. subsidiary Otsuka Pharmaceutical Development and Commercialization, said in a statement. Otsuka will submit complete data and analyses from both trials for scientific publication. The company will also use these findings, along with clinical pharmacology studies and long-term stability data, to build a New Drug Application for centanafadine in this indication. Friday’s ADHD readout comes months after Otsuka and partner Sumitomo Pharma suffered two late-stage defeats in another psychiatric indication. In July 2023, the companies announced that its investigational TAAR1 agonist ulotaront failed the Phase III studies DIAMOND 1 and DIAMOND 2 in schizophrenia patients with acute psychosis. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

RSS Tweet Centanafadine, an investigational compound for the treatment of ADHD, demonstrated statistically significant improvements vs. placebo for primary efficacy endpoints in both clinical trials Otsuka will discuss these results with health authorities Otsuka Pharmaceutical Co., Ltd. (Otsuka) and its U.S. subsidiary, Otsuka Pharmaceutical Development & Commercialization, Inc., today announced positive results of two, 6-week, Phase 3 clinical trials that evaluated the efficacy, safety, and tolerability of centanafadine for the treatment of adolescents and children with attention-deficit/hyperactivity disorder (ADHD). Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor. 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.