Simtriyo (centanafadine) / Otsuka - LARVOL DELTA

Clinically Meaningful Within-Patient Change in Core Attention-Deficit/Hyperactivity Disorder Symptoms in Children and Adolescents Treated With Centanafadine: Results From Two Phase 3 Randomized Clinical Trials. (PubMed, J Atten Disord) - P3 | "Centanafadine was efficacious in children and adolescents with ADHD, providing robust caregiver-reported and self-reported improvements when compared with placebo in the core symptoms of inattention, hyperactivity, and impulsivity."

Clinical • Journal • P3 data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Centanafadine and the Expanding Pharmacologic Landscape of ADHD. (PubMed, J Child Adolesc Psychopharmacol) - No abstract available

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Study to Test the Effects of Centanafadine in Adults With Attention-deficit/Hyperactivity Disorder and Emotional Dysregulation (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Centanafadine (Simtriyo): a triple monoamine reuptake inhibitor for ADHD. (PubMed, Trends Pharmacol Sci) - No abstract available

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Updates in treatment strategies in ADHD (WFSBP 2026) - "Lisdexamfetamine, a prodrug cleaved gradually by red blood cell enzymes, provides smoother pharmacokinetics and lower abuse potential due to slower peak concentrations...OROS-methylphenidate mimics twice-daily dosing through osmotic release, while transdermal methylphenidate bypasses first-pass metabolism and reduces appetite suppression. Serdexmethylphenidate and ion-exchange amphetamine preparations further improve duration and plasma stability...These mechanisms may improve emotional dysregulation and provide faster onset than atomoxetine...Investigational therapies include centanafadine, a triple DAT-NET-SERT inhibitor targeting emotional dysregulation; TAAR-1 agonists, which modulate dopamine and glutamate signaling; and metadoxine extended release, which restores GABA-glutamate balance and may preferentially benefit inattentive ADHD...DAT1 and SERT polymorphisms may predict stimulant or serotonergic treatment response, while COMT Val158Met variants influence..."

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mood Disorders • Psychiatry • Tic Disorders • Tourette Syndrome • COMT

Centanafadine (Simtriyo®): a first-in-class triple reuptake inhibitor approved for attention-deficit/hyperactivity disorder (ADHD). (PubMed, Med Chem Res) - "Unlike flexible phenethylamine stimulants such as (meth)amphetamine (1), which enter presynaptic neurons and actively trigger monoamine release, or piperidine derivatives like methylphenidate (2), which selectively block dopamine and norepinephrine reuptake, centanafadine inhibits all three monoamine transporters without inducing neurotransmitter release. Centanafadine represents a modern medicinal chemistry strategy aimed at managing ADHD symptoms through combined catecholaminergic and serotonergic mechanisms, offering sustained efficacy while potentially mitigating the abuse liability, insomnia, and cardiovascular risks typical of traditional psychostimulants."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

A Study to Test the Effects of Centanafadine in Adults With Attention-deficit/Hyperactivity Disorder and Emotional Dysregulation (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Otsuka…announced that the U.S. Food and Drug Administration (FDA) has granted approval of SIMTRIYO (centanafadine), a once-daily extended-release capsule for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older weighing at least 20kg (Businesswire) - "SIMTRIYO, an NDSRI and central nervous system (CNS) stimulant, is expected to be available later this year following scheduling by the U.S. Drug Enforcement Administration (DEA). The approval is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of SIMTRIYO across adult, adolescent, and pediatric patients. In these Phase 3 clinical studies, SIMTRIYO 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 children and adolescents and the Adult ADHD Investigator Symptom Rating Scale (AISRS) in adults."

FDA approval • Launch US • Attention Deficit Hyperactivity Disorder

Otsuka’s ADHD drug reduces symptoms in Phase IIIb trial (Clinical Trials Arena) - "The trial met its primary endpoint by demonstrating improvements from baseline on the Adult Investigator Symptom Rating Scale (AISRS) total score compared to placebo after eight weeks. Full results will be presented at an upcoming scientific meeting. Centanafadine is currently under regulatory review in the US for the treatment of ADHD in children, adolescents, and adults. The drug has been granted Priority Review by the US Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) target action date of 24 July 2026."

P3 data • PDUFA • Priority review • Attention Deficit Hyperactivity Disorder

Efficacy and Safety of Centanafadine in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Psychopharmacol Bull) - "Centanafadine provides statistically significant and clinically meaningful improvement in ADHD symptoms with generally acceptable tolerability, supporting its role as a non-stimulant treatment option. Further long-term and comparative trials are warranted."

Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Psychiatry

The Evolving Pharmacological Landscape for Paediatric and Adult ADHD. (PubMed, CNS Drugs) - "Considering agents with at least two positive trials for ADHD core symptoms without negative trials, only dasotraline, in children, and centanafadine, in adults, emerged as promising (however, the dasotraline development programme was halted in 2020). This review also includes a discussion of opportunities for advancing the development of novel, effective agents and maximising the benefits of currently available options."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Efficacy of Centanafadine in Treating ADHD-Associated Features in Children Aged 6–17 Years: Pooled Analysis of Short-Term Placebo-Controlled Studies (APA 2026) - P3 | "When compared to placebo, CTN was efficacious with clinically meaningful within-patient change in associated symptoms of ADHD in children and adolescents with ADHD."

Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Psychiatry

A Trial of Centanafadine Long-term Safety in Children and Adolescents With Attention-deficit/Hyperactivity Disorder. (clinicaltrials.gov) - P3 | N=680 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed

Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

COST OF ADVERSE EVENT MANAGEMENT IN CHILDREN, ADOLESCENTS, AND ADULTS WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER IN THE UNITED STATES (ISPOR 2026) - "Pairwise comparisons were conducted between centanafadine and each of lisdexamfetamine dimesylate, atomoxetine hydrochloride, viloxazine, methylphenidate hydrochloride, and guanfacine in children and adolescents, and each of lisdexamfetamine dimesylate, atomoxetine hydrochloride, viloxazine, and methylphenidate hydrochloride in adults. Centanafadine has the potential to reduce AE-related healthcare costs compared with alternative ADHD therapies for children, adolescents, and adults."

Adverse events • Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

P3b Short-term Study of CTN in Patients With ADHD and Comorbid Anxiety (clinicaltrials.gov) - P3 | N=315 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed

Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder

A Trial to Assess How Centanafadine Interacts With Stimulants in the Body (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Completed

Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Efficacy of Centanafadine for Executive Functioning and Learning Problems in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. (PubMed, J Child Adolesc Psychopharmacol) - P3 | "In addition to its impact on the core symptoms of ADHD, centanafadine improved executive functioning, learning problems, and impact on daily tasks in children and adolescents with ADHD."

Clinical • Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

P3b Short-term Study of CTN in Patients With ADHD and Comorbid Anxiety (clinicaltrials.gov) - P3 | N=315 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2027 ➔ Apr 2026

Enrollment closed • Trial completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry • Social Anxiety Disorder

Centanafadine for the treatment of attention-deficit/hyperactivity disorder in adults: a plain language summary of publication. (PubMed, Expert Rev Neurother) - No abstract available

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Trial to Demonstrate the Equivalence of Two Different Strengths of Oral Centanafadine Capsules in Healthy Subjects (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial

A Trial to Compare the Amount of Centanafadine That Enters the Bloodstream for Two Different Formulations of Centanafadine (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial

Centanafadine to treat ADHD in children and adolescents: a plain language summary of publication. (PubMed, Expert Rev Neurother) - No abstract available

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Trial to Assess How Centanafadine Interacts With Stimulants in the Body (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Connecting the dots and finding the way forward: Pharmacological, neuromodulatory, and psychotherapeutic interventions for the complex treatment of adult ADHD. (PubMed, Pharmacol Ther) - "Treatment emphasizes multimodal approaches, with stimulants as first-line pharmacotherapy due to their superior efficacy over non-stimulants like atomoxetine and viloxazine. Novel agents in development, such as centanafadine triple reuptake inhibitor and solriamfetol target core symptoms and comorbidities, showing promising phase III results...Psychotherapeutic options, particularly cognitive-behavioral therapy (CBT)-based interventions, improve symptom management and emotional regulation, often as adjuncts to medication. The review highlights the need for personalized strategies addressing adherence, comorbidity, and long-term outcomes, emphasizing integrated care to mitigate ADHD's lifelong impact."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry

Otsuka Announces FDA Acceptance and Priority Review of New Drug Application for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults (Otsuka Press Release) - "The Prescription Drug User Fee Act (PDUFA) target action date is set for July 24, 2026. The NDA is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across patient populations. In these trials, 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."

FDA filing • PDUFA • Priority review • Attention Deficit Hyperactivity Disorder