OBJECTIVES

Centanafadine (CTN) is a first-in-class norepinephrine, dopamine, serotonin reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder (ADHD). This randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy, safety, and tolerability of CTN versus placebo in children with ADHD.

METHODS

Children 6-12 years of age (inclusive) with a primary diagnosis of ADHD were randomized to weight-based low-dose CTN, weight-based high-dose CTN, or placebo once daily for 6 weeks. The primary endpoint was the change from baseline in the ADHD-RS-5 symptoms total raw score at Week 6.

RESULTS

Of 480 participants randomized (low-dose CTN, n=154; high-dose CTN, n=162; placebo, n=164), 457 received ≥1 dose of study drug and 367 (76%) completed the trial. At Week 6, improvements in ADHD-RS-5 symptoms total raw score were significantly greater with high-dose CTN than with placebo (–16.3 [1.2] vs –10.8 [1.2], p<0.001). High-dose CTN showed separation from placebo as early as Week 1, the first post-baseline timepoint, with the effect maintained throughout the study period. Low-dose CTN did not show statistical significance in the primary endpoint. Treatment-emergent adverse events (TEAEs) occurred in 52/147 (35%) participants in the low-dose CTN group, 61/157 (39%) in the high-dose CTN group, and 39/153 (25%) in the placebo group. The most common TEAEs were decreased appetite (23/457 [5%]), rash (14/457 [3%]), and vomiting (13/457 [3%]). All TEAEs were of mild or moderate severity.

CONCLUSIONS

High-dose CTN was efficacious for treatment of ADHD in children. Both CTN doses were safe and well tolerated.

Subjects:
Attention-Deficit/Hyperactivity Disorder (ADHD), Neurologic Disorders, Psychiatry/Psychology
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Competing Interests

CONFLICT OF INTEREST DISCLOSURES:CLW, NJ, OT, and TS are all currently employees of Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland, USA. TEW has received grant/research support from NIH (NIDA) and Ironshore as a principal investigator; he receives royalties and owns intellectual property with Ironshore, Guilford Press, and Cambridge University Press; is a consultant for Bay Cove Human Services, Gavin Foundation, US Minor/Major League Baseball, US National Football League (ERM Associates), and White Rhone/3D; and is a coeditor for Elsevier Psychiatric Clinics of North America (ADHD). ACC has been a consultant for Aardvark, Arbor, Attentive, Aytu, Ironshore, Lumos, Neos Therapeutics, Neurocentria, Noven, Otsuka, Purdue, Rhodes, Sky, Sunovion, Tris Pharma, Zevra Therapeutics Inc. (previously KemPharm Inc.), Supernus, Corium, and Lumos; has participated on speakers’ bureaus for Ironshore, Neos Therapeutics, Supernus, Takeda Shire, and Tris Pharma; has received research support from Adlon, Akili, Allergan, Arbor, Emalex, Ironshore, Lumos, Neos Therapeutics, Otsuka, Purdue, Rhodes, Servier, Sunovion, Supernus, Takeda Shire, Tris Pharma, US Food and Drug Administration, and Zevra Therapeutics Inc. (previously KemPharm Inc); has received writing support from Arbor, Ironshore, Neos Therapeutics, Otsuka, Takeda Shire, Purdue, Rhodes, Sunovion, and Tris Pharma; and participated on advisory boards for Akili, Arbor, Cingulate, Corium, Ironshore, Otsuka, Purdue, Rhodes, Sunovion, Supernus, Takeda Shire, and Tris Pharma.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © Ward CL et al. Pediatrics Open Science.
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