The findings of two identical phase 3 clinical trials evaluating a first-in-class treatment for adults with ADHD showed promising results, said Otsuka Pharmaceutical recently at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting (26-29 May) in Miami.
The data from the new post hoc, exploratory analyses from two trials evaluating the drug centanafadine, an investigational, first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) in adults with attention-deficit hyperactivity disorder (ADHD), showed that apart from improving core ADHD symptoms, centanafadine was associated with improvements in patient-reported executive function and emotional dysregulation, two clinically meaningful and often under-recognised associated features of ADHD that contribute substantially to patient burden.
The findings add to previously reported positive phase 3 data evaluating centanafadine in adults with ADHD.
Centanafadine is currently under regulatory review in the United States for the treatment of ADHD and has been granted Priority Review by the Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) target action date of 24 July.
“Executive function deficits and emotional dysregulation are challenging aspects of ADHD for many adults and are not always adequately addressed by current treatments,” said Dr Lenard Adler, Director of the adult ADHD programme at NYU Langone Health and an investigator on the studies.
“Improvements across core ADHD symptoms and associated features, as the analyses show, are important considerations in the treatment of adults with ADHD, given the broad and variable symptom experience among patients and the need for approaches that address a range of manifestations of the condition.”
A total of 744 adults were included in the post hoc analyses (centanafadine 200 mg, n=242; centanafadine 400 mg, n=241; placebo n=261). Centanafadine was associated with improvements across measures of executive function compared with placebo, as assessed by the Executive Functioning subscale of the Adult ADHD Self-Report Scale (ASRS) Expanded Version.
At week six, patients treated with centanafadine reported improved executive function from baseline compared with placebo, reflecting reductions in the frequency of patient-reported executive functioning difficulties. This included but was not limited to improvements in aspects like time management, planning and prioritisation, task initiation and completion, and working memory.
Centanafadine was also associated with improved emotional dysregulation compared with placebo. Improvements were observed across emotional dysregulation items, including reductions in emotional over-activity, anger outbursts, as measured by the ASRS Emotional Dyscontrol subscale at week six.
By showing improvements in associated features of ADHD, including executive function and emotional dysregulation, areas of unmet need in ADHD clinical care, these analyses help further characterise centanafadine across a broader range of patient-reported symptoms beyond core symptoms of the condition, said the study team.
“These findings complement our previous research in paediatric and adolescent populations and provide new insights into centanafadine’s clinical profile, while reinforcing its potential to address ADHD more holistically,” said John Kraus, MD, Ph.D, Chief Medical Officer, Otsuka. “The data add to the understanding of centanafadine’s clinical profile as a first-in-class NDSRI.”
The two pivotal trials (NCT03605680, NCT03605836) were randomised, double-blind, placebo-controlled studies designed to evaluate the efficacy, safety, and tolerability of centanafadine sustained-release (SR) tablet in adults aged 18 to 55 with ADHD.
Participants received either centanafadine or placebo over a six-week treatment period. The primary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at week six.
Both centanafadine dose groups demonstrated statistically significant and clinically meaningful improvements versus placebo.
In both studies, centanafadine showed a favourable safety and tolerability profile and a low potential for abuse and dependence, with the most common adverse events including decreased appetite and headache.
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