Centanafadine · program

Centanafadine for Attention-deficit/hyperactivity disorder

Filed (NDA)ActiveOtsuka Pharmaceutical Co., Ltd. (4578.T)
  • Priority Review

NDA for centanafadine (once-daily extended-release capsule) for the treatment of ADHD in children, adolescents, and adults accepted by the FDA with priority review on January 27, 2026; PDUFA target action date July 24, 2026. Supported by four pivotal Phase 3 trials (two adult, one pediatric ages 4-12, one adolescent ages 13-17), all of which met their primary efficacy endpoint.

Data current as of

Development timeline

Filed (NDA)May 2022 – Jul 2026
  1. UpcomingFDA PDUFA target action date for the centanafadine ADHD NDA (children, adolescents, and adults).↗
  2. FDA accepted the NDA and granted priority review; PDUFA target action date set for July 24, 2026.↗
  3. Otsuka submitted the NDA to the U.S. FDA for centanafadine for the treatment of ADHD in children, adolescents, and adults.↗
  4. metAdult Phase 3 trial (NCT03605680) met AISRS primary endpoint at both doses; published Adler et al. 2022, J Clin Psychopharmacol.
  5. metAdult Phase 3 trial (NCT03605836) met AISRS primary endpoint at both doses; published Adler et al. 2022, J Clin Psychopharmacol.
Phase 3Oct 2023
  1. metPediatric Phase 3 trial (children 4-12) met ADHD-RS-5 primary endpoint at week 6; positive topline announced Oct 27, 2023.↗
  2. metAdolescent Phase 3 trial (13-17) met ADHD-RS-5 primary endpoint at week 6 (high dose); positive topline announced Oct 27, 2023.↗

Readouts

  • July 24, 2026AnticipatedRegulatory

    FDA PDUFA target action date for the centanafadine ADHD NDA (children, adolescents, and adults). ↗

  • 2023-10-27ReportedTopline datametNCT05428033

    Pediatric Phase 3 trial (children 4-12) met ADHD-RS-5 primary endpoint at week 6; positive topline announced Oct 27, 2023. ↗

  • 2023-10-27ReportedTopline datametNCT05257265

    Adolescent Phase 3 trial (13-17) met ADHD-RS-5 primary endpoint at week 6 (high dose); positive topline announced Oct 27, 2023. ↗

  • 2022-05-01ReportedFull resultsmetNCT03605680

    Adult Phase 3 trial (NCT03605680) met AISRS primary endpoint at both doses; published Adler et al. 2022, J Clin Psychopharmacol.

  • 2022-05-01ReportedFull resultsmetNCT03605836

    Adult Phase 3 trial (NCT03605836) met AISRS primary endpoint at both doses; published Adler et al. 2022, J Clin Psychopharmacol.

Clinical trials in Attention-deficit/hyperactivity disorder

NCT07087327Phase 3Recruitingn=180

A Long-term Trial of EB-1020 in Pediatric Patients With ADHD

Started Sept 2025· Primary completion Aug 2027· 📍 1 site across 1 country (Japan)

NCT07086313Phase 2/3Recruitingn=315

A Trial to Evaluate the Efficacy and Safety of EB-1020 in Pediatric Patients With ADHD

Started Sept 2025· Primary completion Aug 2027· 📍 1 site across 1 country (Japan)

NCT06926829Phase 3Recruitingn=180

A Long-term Trial of EB-1020 in Adult Patients With ADHD

Started Jun 2025· Primary completion Dec 2027· 📍 1 site across 1 country (Japan)

NCT06931080Phase 2/3Recruitingn=630

Evaluation of the Efficacy and Safety of EB-1020 in Adult ADHD Patients

Started Apr 2025· Primary completion Dec 2027· 📍 1 site across 1 country (Japan)

NCT05428033Phase 3Completedn=574

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Efficacy and Safety of Once Daily Centanafadine Capsules for the Treatment of Children With Attention-deficit/Hyperactivity Disorder (ADHD)

Started Jul 2022· Primary completion Mar 2025· 📍 1 site across 1 country (United States)

metprimaryChange from baseline in ADHD-RS-5 symptoms total raw score at Week 6 (children ages 4-12) — Average of both doses vs placebo p=0.0039; high dose p=0.0008 (average p=0.0039; high dose p=0.0008)

Once-daily centanafadine capsules met the primary endpoint in children: statistically significant improvement in ADHD-RS-5 at week 6 vs placebo (average of both doses and high dose); low dose did not reach significance. Topline reported Oct 27, 2023.

NCT05257265Phase 3Completedn=459

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Efficacy and Safety of Once Daily Centanafadine Capsules for the Treatment of Adolescents With Attention-deficit/Hyperactivity Disorder

Started Feb 2022· Primary completion Sept 2023· 📍 1 site across 1 country (United States)

metprimaryChange from baseline in ADHD-RS-5 symptoms total raw score at Week 6 (adolescents ages 13-17) — Centanafadine 328.8 mg: -18.50 vs placebo -14.15 (LS mean); high-dose p=0.0006; average of both doses p=0.0099 (high dose (328.8 mg) p=0.0006; 164.4 mg did not meet)

Once-daily centanafadine capsules met the primary endpoint in adolescents: high dose (328.8 mg) significantly improved ADHD-RS-5 at week 6 vs placebo; low dose (164.4 mg) did not. Published in JAACS/JAACAP 2025.

NCT03605680Phase 3Completedn=604

A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy, Safety, & Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder

Started Jan 2019· Primary completion Apr 2020· 📍 1 site across 1 country (United States)

metprimaryChange from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Day 42 — Centanafadine 200 mg: -10.1; 400 mg: -9.73; placebo: -6.98 (LS mean change) (200 mg p=0.0193; 400 mg p=0.0392)

Both centanafadine doses (200 mg and 400 mg total daily dose, BID) significantly reduced AISRS scores vs placebo at Day 42. Primary endpoint met for both doses (Adler et al. 2022, J Clin Psychopharmacol).

NCT03605836Phase 3Completedn=590

A Phase 3, Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder

Started Jan 2019· Primary completion May 2020· 📍 1 site across 1 country (United States)

metprimaryChange from baseline in ADHD Investigator Symptom Rating Scale (AISRS) total score at Day 42 — Centanafadine 200 mg: -12.1; 400 mg: -12.5; placebo: -8.07 (LS mean change); LS mean difference -4.01 (200 mg) and -4.42 (400 mg) (200 mg p=0.0021; 400 mg p=0.0009)

Both centanafadine doses significantly reduced AISRS scores vs placebo at Day 42. Primary endpoint met for both doses (Adler et al. 2022, J Clin Psychopharmacol).

NCT02144415Phase 1Completedn=80

A Study to Evaluate the Abuse Potential of EB-1020 Immediate-Release in Healthy Recreational Stimulant Users

Started May 2014· Primary completion Jul 2014· 📍 1 site across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
Centanafadine sustained-release tabletsustained-release tablet
200-400 mg total daily dose, divided twice daily (morning and 4-6 h later); titrated from 200 mg TDD to target 400 mg TDD
OralTwice dailyt½ 4.5 h · Tmax 2 h

Mechanism of action (compound-wide)

Triple monoamine reuptake inhibitor (norepinephrine, dopamine, and serotonin reuptake inhibitor; NDSRI). It inhibits reuptake at NET, DAT, and SERT with in vitro IC50 values of 6 nM, 38 nM, and 83 nM respectively (rank order of potency NET > DAT > SERT), increasing synaptic availability of all three monoamines.

TargetActionAffinity
NETprimarySLC6A2Reuptake inhibitorIC50 6 nMⓘ
DATSLC6A3Reuptake inhibitorIC50 38 nMⓘ
SERTSLC6A4Reuptake inhibitorIC50 83 nMⓘ

← Full Centanafadine compound page (identity, identifiers, all indications)

Sources

  1. 52-Week Open-Label Safety and Tolerability Study of Centanafadine Sustained Release in Adults With Attention-Deficit/Hyperactivity Disorder — PMC / Journal
  2. Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial — Journal of the American Academy of Child & Adolescent Psychiatry
  3. Centanafadine SR Tablets in Adults With ADHD (NCT03605680) — ClinicalTrials.gov
  4. Centanafadine SR Tablets in Adults With ADHD (NCT03605836) — ClinicalTrials.gov
  5. clinicaltrials.gov — clinicaltrials.gov
  6. clinicaltrials.gov — clinicaltrials.gov
  7. clinicaltrials.gov — clinicaltrials.gov
  8. clinicaltrials.gov — clinicaltrials.gov
  9. clinicaltrials.gov — clinicaltrials.gov
  10. Once Daily Centanafadine Capsules in Adolescents With ADHD (NCT05257265) — ClinicalTrials.gov
  11. Once Daily Centanafadine Capsules in Children With ADHD (NCT05428033) — ClinicalTrials.gov
  12. Otsuka Announces FDA Acceptance and Priority Review of New Drug Application for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults — Otsuka Pharmaceutical
  13. Otsuka Pharmaceutical Announces Positive Topline Results from Two Pivotal Phase 3 Trials of Centanafadine as a Treatment for Adolescents and Children with ADHD — Otsuka Pharmaceutical
  14. Otsuka Pharmaceutical Submits New Drug Application to U.S. FDA for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults — Otsuka Pharmaceutical
  15. Structural basis for pharmacotherapeutic action of triple reuptake inhibitors — Nature Communications (PMC)