Centanafadine promising therapy for adults with attention-deficit or hyperactivity disorder

USA: Centanafadine has demonstrated efficacy, safety, and well tolerability, with a limited abuse potential for the treatment of ADHD, states  2 phase 3 randomized controlled trials results published in the Journal of Clinical Psychopharmacology. Thus, centanafadine can be considered a valuable nonstimulant tool for the treatment of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral condition affecting an estimated 4.4% of adults in the United States. Centanafadine, an inhibitor of norepinephrine, dopamine, and serotonin reuptake transporters is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD). It is expected to effectively resolve the core symptoms of ADHD, show a favourable tolerability profile, and have a short titration curve when received as a therapeutic dose within 2 weeks of treatment initiation or sooner.

Dr Lenard Adler, NYU Grossman School of Medicine, New York and colleagues conducted 2 phase 3 randomized, double-blind, placebo-controlled, parallel-group studies of 200 mg/d or 400 mg/d centanafadine sustained-release tablets versus placebo with adults (18–55 years of age) diagnosed with ADHD. The change in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score and the Clinical Global Impression–Severity of Illness Scale, respectively from baseline at day 42 was the primary and key secondary efficacy endpoints.

Subjects randomized in study 1 (centanafadine 200 mg/d, n = 149; centanafadine 400 mg/d, n = 149; placebo, n = 148) and study 2 (centanafadine 200 mg/d, n = 145; centanafadine 400 mg/d, n = 143; placebo, n = 142) had moderate to severe ADHD across both studies.

Key findings of the trial are,

• Statistically significant least-squares mean differences in AISRS total score were observed in favour of centanafadine versus placebo in study 1  and study 2.

• Effect sizes versus placebo were −0.28, −0.24 for 200 mg/d, 400 mg/d respectively in study 1 and −0.37, −0.40 for 200 mg/d, 400 mg/d respectively in study 2.

• The overall rate of treatment-emergent adverse events (TEAEs) was low, but there was a small increase in TEAE occurrence with increasing doses.

• Incidences of serious TEAEs and abuse potential–related AEs were low.

Investigators concluded that these are the first large-scale studies that demonstrated the efficacy and safety profiles of 200 mg/d and 400 mg/d centanafadine in adults with ADHD. Also, it was found to be well-tolerated, with a limited abuse potential across the clinical trial program.

Future studies should determine the long-term safety profile of centanafadine and define the efficacy profile of centanafadine as compared with other available therapies for ADHD.

Reference:

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. J Clin Psychopharmacol. 2022 Jun 2. doi: 10.1097/JCP.0000000000001575. Epub ahead of print. PMID: 35652746.