Centanafadine (Simtriyo) — Primary Literature Archive
Assembled by Ryan S. Sultan, MD, Assistant Professor of Clinical Psychiatry, Columbia University Irving Medical Center · Last updated
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What this is. Every peer-reviewed clinical trial publication supporting the FDA approval of centanafadine (Simtriyo), collected in one place with full citations and hosted for direct download. Four carry Creative Commons licenses permitting redistribution. The remaining documents are provided for educational use with permission from the authors and publishers. All files are the versions of record, unmodified, and attribution belongs to the original authors and journals. For the clinical analysis of these trials, see Centanafadine: A Deep Analysis of the Primary Literature. |
Hosted for Download (Creative Commons Licensed)
These four papers carry Creative Commons licenses permitting redistribution with attribution. Each is reproduced here unmodified, with its original license stated. Attribution is to the original authors and journals, not to this site.
| Trial | Citation | License | Download |
|---|---|---|---|
| Phase 2, adults Dose-finding |
Wigal SB, Wigal T, Hobart M, Madera JJ, Baker RA, Kohegyi E, McKinney A, Wilens TE. Safety and Efficacy of Centanafadine Sustained-Release in Adults With Attention-Deficit Hyperactivity Disorder: Results of Phase 2 Studies. Neuropsychiatric Disease and Treatment. 2020;16:1411–1426. doi:10.2147/NDT.S242084 |
CC BY-NC 3.0 | PDF 610 KB |
| Phase 3, adults 2 pivotal trials NCT03605680 NCT03605836 |
Adler LA, Adams J, Madera-McDonough J, Kohegyi E, Hobart M, Chang D, Angelicola M, McQuade R, Liebowitz M. Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. Journal of Clinical Psychopharmacology. 2022;42(5):429–439. doi:10.1097/JCP.0000000000001575 |
CC BY-NC-ND 4.0 | PDF 1.2 MB |
| Phase 3, adolescents Ages 13–17 NCT05257265 |
Ward CL, Childress AC, Jin N, Turkoglu O, Skubiak T, Wilens TE. Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial. Journal of the American Academy of Child & Adolescent Psychiatry. 2025. doi:10.1016/j.jaac.2025.06.023 |
CC BY 4.0 | PDF 837 KB |
| Phase 3, children Ages 6–12 NCT05428033 |
Ward CL, Wilens TE, Jin N, Turkoglu O, Skubiak T, Childress AC. Efficacy and Safety of Centanafadine for ADHD Treatment in Children: A Randomized Clinical Trial. Pediatrics Open Science. 2025. doi:10.1542/pedsos.2024-000349 |
CC BY 4.0 | PDF 789 KB |
License notes. CC BY 4.0 permits redistribution and adaptation with attribution. CC BY-NC 3.0 and CC BY-NC-ND 4.0 permit redistribution for non-commercial purposes with attribution; the ND term additionally forbids modification, so the Adler 2022 PDF is reproduced exactly as published. This archive page carries no advertising and no commercial call to action, consistent with the non-commercial terms.
Indirect Comparisons and Reference Documents
These are hosted for educational use with permission. The two matching-adjusted indirect comparisons (MAICs) are the only published attempts to position centanafadine against active comparators — no head-to-head trial against any stimulant or non-stimulant exists. Both are Otsuka-funded, and both should be read with that in mind; see the analysis for a detailed appraisal of their validity.
| Document | Citation | Status | Download |
|---|---|---|---|
| MAIC vs lisdexamfetamine, atomoxetine, viloxazine ER | Schein J, Cloutier M, Gauthier-Loiselle M, Catillon M, Xu C, Chan D, Childress A. Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release. Journal of Managed Care & Specialty Pharmacy. 2024;30(6):528–540. JMCP.org |
© 2024 Academy of Managed Care Pharmacy. Educational use with permission. | PDF 426 KB |
| MAIC vs methylphenidate | Schein J, Catillon M, Xu C, Qu A, Lemyre A, Gauthier-Loiselle M, Cloutier M, Childress A. 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. The Canadian Journal of Psychiatry. 2025;70(8):629–638. doi:10.1177/07067437251342279 |
© 2025 The Author(s), SAGE. Educational use with permission. | PDF 751 KB |
| Simtriyo product monograph Consumer reference, not primary literature |
Simtriyo (centanafadine): ADHD Uses, Dosage & Side Effects. Consumer drug monograph, medically reviewed by Melisa Puckey, BPharm. Updated July 27, 2026. drugs.com/simtriyo.html |
Third-party consumer monograph. Convenience copy. | PDF 194 KB |
| Simtriyo prescribing information The authoritative source |
Otsuka America Pharmaceutical, Inc. SIMTRIYO (centanafadine) extended-release capsules. Full Prescribing Information. Revised 7/2026. Contains the boxed warnings, the pediatric suicidality analysis, and the pharmacokinetic data absent from all of the papers above. | Manufacturer document, revised periodically. | Official PI linked, always current |
The prescribing information is linked rather than copied on purpose: labels are revised, and a stale local copy of a document carrying two boxed warnings would be a genuine safety problem. Always read the current version.
Trials at a Glance
| Phase | Population | N randomized | Doses studied | Duration | Primary endpoint |
|---|---|---|---|---|---|
| Phase 2a (single-blind) NCT01939353 | Adult males 18–55 | 41 treated | SR, BID, titrated to 500 mg/d | 4 weeks | ADHD-RS-IV total |
| Phase 2b (crossover) NCT02547428 | Adults 18–60 | 85 randomized | SR, BID, 400 / 600 / 800 mg/d | 3 + 3 weeks | ADHD-RS-IV total |
| Phase 3 NCT03605680 | Adults 18–55 | 466 | SR tablets, BID, 200 or 400 mg/d | 6 weeks | AISRS total, day 42 |
| Phase 3 NCT03605836 | Adults 18–55 | 440 | SR tablets, BID, 200 or 400 mg/d | 6 weeks | AISRS total, day 42 |
| Phase 3 NCT05257265 | Adolescents 13–17 | 459 | XR capsules, QD, 164.4 or 328.8 mg, no titration | 6 weeks | ADHD-RS-5 total, week 6 |
| Phase 3 NCT05428033 | Children 6–12 (ages 4–5 cohort ongoing) | 480 | XR capsules, QD, weight-based 41.1–328.8 mg | 6 weeks | ADHD-RS-5 total, week 6 |
| Phase 3b | Adults, ADHD + anxiety | Topline only | XR 280 mg QD | 8 weeks | AISRS total, week 8 |
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Two traps when reading these papers side by side. 1. Two dose-numbering systems for the same doses. The trials report centanafadine hydrochloride; the label reports free base. 164.4 mg = 140 mg, 246.6 mg = 210 mg, 328.8 mg = 280 mg. The adolescent trial's "328.8 mg" and the label's "280 mg" are the same dose. It is easy to double-count doses across sources. 2. The adults were studied on a different formulation and schedule than the one approved. Both adult Phase 3 trials used sustained-release tablets twice daily (200 or 400 mg total daily dose). Both pediatric trials used the once-daily extended-release capsule. The marketed product is the once-daily XR capsule, and the approved adult regimen (210 mg → max 280 mg once daily) was bridged to adult efficacy by pharmacokinetic exposure-matching — it is not the regimen any positive adult Phase 3 trial actually tested. Both points are developed in the analysis. |
Placebo response is not comparable across these trials either. The two adult trials used a one-week single-blind placebo run-in and excluded placebo responders — 24.1% of run-in participants never entered the double-blind phase. Neither pediatric trial used a run-in. Placebo-arm symptom reduction was 17.7% and 21.4% in the adult trials versus 38.4% in adolescents and 25.0% in children. Placebo-subtracted differences from these trials cannot be compared at face value.
Phase 3b (ADHD with Comorbid Anxiety) — Topline Only
A Phase 3b trial of centanafadine XR 280 mg once daily in adults with ADHD and comorbid anxiety met its primary endpoint. Reported topline results: AISRS total score change at week 8 of −19 versus −13 for placebo (a 6-point placebo-subtracted difference), and on the key secondary endpoint, HAM-A total score change of −12.5 versus −10.6 (a 1.92-point difference).
No peer-reviewed publication exists for this trial yet. These figures come from the manufacturer's press release and have not been through peer review; the full results, including confidence intervals and adverse event data, are not publicly available. Source: Otsuka Announces Positive Phase 3b Results for Centanafadine in Adults with ADHD and Comorbid Anxiety. Otsuka US press release.
Reuse and Corrections
The hosted PDFs are the publishers' versions of record, unmodified. If you are a rights holder and believe a document here should not be, contact me and I will remove it promptly. If you spot an error in a citation or in my analysis, I want to know — corrections are made and dated.
Citing this archive: cite the original papers, not this page. If you need to reference the collection itself: Sultan RS. Centanafadine Primary Literature Archive. ryansultan.com/literature/centanafadine/. Accessed [date].
Related
- Centanafadine: A Deep Analysis of the Primary Literature — effect sizes, time course, dose-response, mechanism, and comparison with methylphenidate, amphetamine, atomoxetine, bupropion, and nicotinic agents
- Centanafadine (Simtriyo): What the Label Actually Says — the prescribing information, dual boxed warnings, and DEA scheduling
- ADHD Pharmacology and the Natural Course of Illness
- ADHD Medication Guide
- Dr. Sultan's Publications