• Centanafadine is an investigational compound for the treatment of ADHD in children, adolescents, and adults. It is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI).
• In four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across pediatric and adult patient populations, centanafadine demonstrated statistically significant efficacy for the core symptoms of inattention and hyperactivity-impulsivity in ADHD.
• Clinical and preclinical data suggest centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence.
• ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity.
• Although historically seen as a childhood disorder, research suggests that many individuals diagnosed with ADHD in childhood continue to experience symptoms into adulthood, with some patients experiencing significant impairment.
• ADHD is often not diagnosed until adulthood, with an estimated 15.5 million adults in the U.S. currently diagnosed.

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Otsuka Pharmaceutical Development & Commercialization, Inc. announce the filing of a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for centanafadine, once daily extended release capsules, a novel norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI), for the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents, and adults. The NDA submission is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across patient populations^1,2,3.

"As an innovator in mental health, we are pleased to take this important step forward in the hope of providing a novel treatment option to patients living with ADHD," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "Centanafadine represents a first in class mechanism of action among available ADHD therapies, and if approved, may expand the range of options available to those managing this complex condition. We are grateful to the patients and caregivers for their participation in these trials."

In Phase 3 clinical studies with children, adolescents, and adults, centanafadine demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo, as measured by the ADHD Rating Scale-5 (ADHD-RS-5) in adolescents and children, and the ADHD Investigator Symptom Rating Scale (AISRS) in adults. Centanafadine was generally well tolerated across studies, with the most common adverse events including decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence in children and adolescents, and decreased appetite and headache in adults^1,2,3.

About the Phase 3 Clinical Trial Program

The Phase 3 program for centanafadine provides a robust clinical evaluation of the first investigational NDSRI ADHD therapy. The clinical program consists of four different pivotal Phase 3 trials that evaluated the efficacy and safety of centanafadine across children, adolescents, and adults^1,2,3.

The pivotal Phase 3 trial in children (NCT05428033) was a randomized, double-blind, three-arm, fixed-dose study evaluating the efficacy, safety, and tolerability of centanafadine in children aged 4 to 12 years with ADHD. Participants received a weight-based high dose, low dose, or placebo for 6 weeks. The primary endpoint was the change from baseline in ADHD-RS-5 total score at Week 6. The high-dose group demonstrated statistically significant improvement versus placebo, while the low-dose group did not reach statistical significance. Centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most frequently reported adverse events including decreased appetite, rash, and vomiting¹.

The pivotal Phase 3 trial in adolescents (NCT05257265) was a randomized, double-blind, three-arm, fixed-dose study designed to evaluate the efficacy, safety, and tolerability of centanafadine in adolescents aged 13 to 17 years with ADHD. Participants received either a high dose, low dose, or placebo over a 6-week treatment period. The primary endpoint was change from baseline in the ADHD Rating Scale-5 (ADHD-RS-5) total score at Week 6. The high-dose group achieved statistically significant and clinically meaningful reductions in ADHD symptoms compared with placebo. Centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most common adverse events including decreased appetite, nausea, headache, and rash².

The two pivotal Phase 3 trials in adults (NCT03605680, NCT03605836) were randomized, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of centanafadine sustained-release (SR) tablet in adults aged 18 to 55 years with ADHD. Participants received either centanafadine 200 mg/day, 400 mg/day, or placebo over a 6-week treatment period. The primary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6. Both centanafadine dose groups demonstrated statistically significant and clinically meaningful improvements versus placebo. In both studies, centanafadine showed a favorable safety and tolerability profile and a low potential for abuse and dependence, with the most common adverse events including decreased appetite and headache³.

About Attention-Deficit Hyperactivity Disorder (ADHD)

ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity⁴. It affects approximately 7 million children in the U.S. and an estimated 15.5 million adults, according to the Centers for Disease Control and Prevention (CDC)^5,6.

About Centanafadine

Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). Clinical studies have shown that centanafadine significantly reduces core symptoms of ADHD in children, adolescents, and adults, with a favorable safety and tolerability profile and low potential for abuse.

About Otsuka

Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide. For further information, please visit www.otsuka.co.jp/en/