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

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

A Trial of Centanafadine Efficacy and Safety in Children With Attention-deficit/ Hyperactivity Disorder (ADHD) (clinicaltrials.gov) - P3 | N=574 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2025 ➔ Mar 2025 | Trial primary completion date: Oct 2025 ➔ Mar 2025

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

Conducting clinical trials with self-collection of pharmacokinetic samples: Experience from an exploratory, phase 1, open-label trial of centanafadine SR in healthy individuals. (PubMed, Contemp Clin Trials Commun) - "Participants favored self-collection over staff collection, having visits in their own location, and would consider participation in similar future research. Results from this decentralized PK trial, with remote, in-home sample collection and monitoring, demonstrated the potential feasibility of this study design."

Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease

At-Home Self-Collection of Pharmacokinetic Data: Design and Results From a Phase 1 Open-Label Feasibility Trial. (PubMed, Clin Pharmacol Drug Dev) - "We present the design of a Phase 1, open-label, fixed-sequence, PK trial that aimed to compare the timing accuracy of participant- versus staff-collected data, and we provide safety and tolerability outcomes for centanafadine treatment...No adverse events were related to treatment. Overall, results support the feasibility of at-home collection of PK samples, ECGs, and vital signs."

Journal • P1 data • PK/PD data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Treatment Preferences of Physicians Treating Adult Patients with Attention-Deficit/Hyperactivity Disorder in the United States and Canada: A Discrete Choice Experiment. (PubMed, Neurol Ther) - "Efficacy was the most important single attribute for physicians treating adult patients with ADHD in both the US and Canada; however, the risks of AEs taken together had greater relative importance than efficacy alone among US but not Canadian physicians. These findings highlight potential discrepancies in physician and patient preferences based on existing evidence and underscore the importance of shared decision-making, which may in turn increase patients' treatment satisfaction."

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

Conners 3-Parent and -Self-Report Short Hyperactivity/Impulsivity and Inattention Content Scales in Adolescents With ADHD Treated With Centanafadine (AACAP 2024) - P3 | "High-dose CTN (328.8 mg) showed an early and sustained impact on improving core H/I and I symptoms in adolescents vs placebo for both caregiver and adolescent perceptions of symptom improvement.ADHD, RCT, SAC"

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

Efficacy and Safety of Once-Daily Extended-Release Centanafadine for the Treatment of ADHD in Children Aged 6–12 Years (CADDRA ADHD 2024) - P3 | "Overall, 367/480 (76.5%) randomized patients completed the study (mean age 9.2 years; 58% male). Change from baseline in ADHD-RS-5 symptoms total raw score at Week 6 was ‒16.3 for CTN high dose versus ‒10.8 for placebo (P=0.0008), with improvement seen from Week 1 (P=0.0009). Low-dose CTN did not meet the primary endpoint."

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

Efficacy and Safety of Once-Daily Extended-Release Centanafadine for the Treatment of ADHD in Adolescents Aged 13–17 Years (CADDRA ADHD 2024) - P3 | "Overall, 371/459 (80.8%) randomized patients completed the study (mean age 14.7 years; 59% male). The change from baseline in ADHD-RS-5 symptoms total raw score at Week 6 was ‒18.5 for CTN 328.8mg versus ‒14.2 for placebo (P=0.0006), with benefit seen from Week 1 (P=0.001). CTN 164.4mg did not meet the primary endpoint."

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