centanafadine SR (EB-1020) / Otsuka - LARVOL DELTA

A Trial to Characterize Differences in Blood Levels of Different Lots of Centanafadine QD XR and to Understand the Effect of Food on Blood Levels (clinicaltrials.gov) - P1 | N=174 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial

Otsuka Pharmaceutical Submits New Drug Application to U.S. FDA for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults (Businesswire) - "The NDA submission is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of centanafadine across patient populations."

FDA filing • Attention Deficit Hyperactivity Disorder

Editorial: Centanafadine for Adolescents With Attention-Deficit/Hyperactivity Disorder: Is a Broader Mechanism of Action Better? (PubMed, J Am Acad Child Adolesc Psychiatry) - No abstract available

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

Efficacy of Centanafadine for the Treatment of ADHD in a Pediatric Population Across Disease Severities (AACAP 2025) - "In a pediatric population, high-dose CTN demonstrated greater improvement from baseline despite baseline severity of ADHD.ADOL, ADHD, ND"

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

Prior Treatment With Stimulants Did Not Impact Response to Centanafadine in a Pediatric Population With ADHD (AACAP 2025) - "The data shown here suggest that high-dose CTN is efficacious in children and adolescents with ADHD and previous stimulant treatment.ADOL"

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

P3b Short-term Study of CTN in Patients With ADHD and Comorbid Anxiety (clinicaltrials.gov) - P3 | N=308 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial primary completion date: Sep 2027 ➔ Jun 2026

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

Potential treatments for attention-deficit/Hyperactivity disorder: a focus on phase III trials. (PubMed, Expert Opin Pharmacother) - "Stimulant medications, such as methylphenidate and amphetamine derivatives, and non-stimulant medications, such as atomoxetine, guanfacine, clonidine, and viloxazine, are considered the cornerstones of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD)...We highlight four promising candidates: centanafadine, solriamfetol, CTx-1301, and NRCT-101SR...Additionally, multi-phase extended-release formulations may improve adherence and enhance symptom control throughout the day. As phase III data become available, these agents have the potential to redefine ADHD treatment paradigms."

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

A Long-term Trial of EB-1020 in Pediatric Patients With ADHD (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

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

A Trial to Evaluate the Efficacy and Safety of EB-1020 in Pediatric Patients With ADHD (clinicaltrials.gov) - P2/3 | N=315 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

New P2/3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial. (PubMed, J Am Acad Child Adolesc Psychiatry) - P3 | "Centanafadine 328.8 mg was efficacious for ADHD treatment in adolescents. Both doses were generally safe and well tolerated."

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

52-Week Open-Label Safety and Tolerability Study of Centanafadine Sustained Release in Adults With Attention-Deficit/Hyperactivity Disorder. (PubMed, J Clin Psychopharmacol) - "Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD."

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

Comparison of the Pharmacological and Behavioral Profiles of Centanafadine and Methylphenidate – Implications for Safety and Abuse Potential (CPDD 2025) - "CTN increased DA and 5-HT neurotransmission in vSTR. Methylphenidate only increased DA neurotransmission. No CTN dose produced locomotor activation, whereas all doses of methylphenidate that increased DA efflux also induced locomotor activity."

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

A Matching-Adjusted Indirect Comparison (MAIC) of Centanafadine versus Methylphenidate Hydrochloride in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): Short-Term Safety and Efficacy Outcomes: Comparaison indirecte ajustée par appariement (MAIC) entre centanafadine et le chlorhydrate de méthylphénidate chez les adultes atteints d'un trouble déficitaire de l' (PubMed, Can J Psychiatry) - P3 | "ObjectivesTo compare the short-term safety and efficacy of centanafadine, an investigational treatment, versus long-acting controlled-release methylphenidate hydrochloride (methylphenidate, Foquest®) among adult patients with attention-deficit/hyperactivity disorder (ADHD), using matching-adjusted indirect comparison (MAIC).MethodsThis anchored MAIC used pooled individual patient data (IPD) from two centanafadine trials (NCT03605680, NCT03605836) and published aggregate data from one methylphenidate trial (NCT02139124). There was no significant difference in efficacy across treatments as measured by the mean change from baseline in AISRS/ADHD-RS-5 score.ConclusionsIn this MAIC, centanafadine was associated with a lower risk of insomnia and comparable (i.e., nondifferent) efficacy compared to methylphenidate at Week 4. Information on the comparative safety and efficacy of ADHD treatments in the adult population will help inform personalized treatment decisions..."

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

JUNIPER: Trial of Centanafadine Efficacy and Safety as Monotherapy or as Adjunct to SSRI in Adults With Major Depressive Disorder (clinicaltrials.gov) - P2 | N=337 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Completed

Monotherapy • Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Randomized Thorough QT Trial Using Concentration-QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization. (PubMed, Clin Pharmacol Drug Dev) - "This double-blind, placebo- and moxifloxacin-controlled, 3-period crossover trial evaluated the effects of centanafadine (EB-1020) and its metabolite (EB-10601) on cardiac repolarization in 30 healthy adults (18-65 years). No serious treatment-emergent adverse events or deaths were reported. Centanafadine was generally safe and well-tolerated, with no clinically meaningful effect on cardiac repolarization."

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

Clinically Meaningful Within-Patient Change in ADHD Symptoms Following Centanafadine Treatment in Adults With ADHD (APA 2025) - "CTN was efficacious, with significant clinically meaningful within-patient change in ADHD symptoms in adults with ADHD. This study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc."

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

Clinically Meaningful Caregiver-Rated Improvements in ADHD Symptoms Following 6 Weeks of Centanafadine Treatment in Pediatric Patients With ADHD (APA 2025) - "High-dose CTN was efficacious, and safe and well tolerated, with significant clinically meaningful within-patient change in ADHD symptoms as measured by the Conners 3-PS for the population studied. This study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc."

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

Clinically Meaningful Within-Patient Change in ADHD Symptoms Following Centanafadine Treatment in Pediatric Patients With ADHD (APA 2025) - "High-dose CTN was efficacious, and safe and well tolerated with significant clinically meaningful within-patient change in ADHD symptoms for the population studied. This study was supported by Otsuka Pharmaceutical Development & Commercialization, Inc."

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

A Trial of Centanafadine Efficacy and Safety in Adults With Attention-deficit/Hyperactivity Disorder and Comorbid Anxiety (clinicaltrials.gov) - P3 | N=308 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

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

Improvement in Caregiver-Rated Executive Functioning Following Centanafadine Treatment in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder (PAS 2025) - "In patients treated with high-dose CTN, a greater difference than placebo in the mean change from baseline at Week 6 in Executive Functioning T-score was observed for both children (mean change [standard error]: CTN, −11.3 [1.12]; placebo, −6.8 [1.11], P=0.0026) and adolescents (CTN, −13.0 [1.01]; placebo, −8.1 [0.99], P=0.0003). Significant improvements with high-dose CTN versus placebo were observed as early as Week 1 in children (P=0.0073) and Week 2 in adolescents (P=0.0047), with effects sustained or further improved with continued treatment. Adverse events were generally mild to moderate."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Mental Retardation • Pediatrics • Psychiatry

Efficacy of Centanafadine on the Conners 3 Learning Problems Content Scale in Pediatric Patients With Attention-Deficit/Hyperactivity Disorder (PAS 2025) - "Overall, 76.5% (367/480) of children (mean age 9.2y, 58.3% male) and 80.8% (371/459) of adolescents (mean age 14.7y, 59.3% male) completed their respective studies. At Week 6 a significant mean change from baseline in Learning Problems Content Scale T-scores was observed with high-dose CTN compared to placebo in children (mean change [standard error]: −8.2 [0.95] vs placebo −2.8 [0.93], P< 0.0001) and in adolescents (PS: −8.0 [0.92] vs placebo −3.1 [0.90], P< 0.0001; SRS: −6.1 [0.86] vs placebo −2.5 [0.85], P=0.0023). Low-dose CTN also demonstrated a significant effect compared to placebo at Week 6 in children (−5.47 [0.97] vs placebo −2.81 [0.93], P=0.0393)."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Mental Retardation • Pediatrics • Psychiatry

Evaluation of the Efficacy and Safety of EB-1020 in Adult ADHD Patients (clinicaltrials.gov) - P2/3 | N=630 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

New P2/3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Trial of Centanafadine Long-term Safety in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P3 | N=680 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Mar 2026 | Trial primary completion date: Jan 2027 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Long-term Trial of EB-1020 in Adult Patients With ADHD (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

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

A Trial of Centanafadine Efficacy and Safety in Children With Attention-deficit/ Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P3 | N=574 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed

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