Japanese pharmaceutical company Otsuka Pharma and its U.S. subsidiary Otsuka Pharmaceutical Development and Commercialization Corp. recently announced the positive results of two 6-week phase III clinical trials evaluating oral centanafadine for the treatment of attention deficit hyperactivity disorder (ADHD) in adults result.
Centanafadine is a triple reuptake inhibitor of serotonin, norepinephrine, and dopamine, and is currently being developed for the treatment of adult ADHD. Otsuka also plans to investigate the drug in treating children with ADHD and discuss the next steps with the US Food and Drug Administration (FDA).
In these two phase III studies, approximately 900 adult patients between the ages of 18 and 55 years who were diagnosed with ADHD were randomly divided into 2 groups. These studies are randomized, double-blind, multi-center, placebo-controlled, parallel group studies. Patients were randomly assigned in a 1:1:1 ratio and received centanafadine at a dose of 100 mg or 200 mg twice daily (total daily dose of 200 mg or 400 mg, respectively), or placebo twice daily. Currently, Otsuka is conducting a long-term safety and tolerability study of centanafadine with a total daily dose of 400 mg, and it is expected that the latest results will be obtained in 2021.
centanafadine chemical structural formula (Image source: Wikipedia)
In these two phase III studies, the data showed that centanafadine at oral doses of 200 mg and 400 mg once daily showed statistically significant improvements in both the primary and critical secondary efficacy endpoints compared to placebo.
The primary efficacy endpoint data showed that in two studies, the 200 mg and 400 mg doses of centanafadine showed statistically significant changes from baseline to day 42 in the total score of the Adult ADHD Investigator's Symptom Rating Scale (AISRS) compared to placebo. Significant improvement (p<0.05 in the first study and p<0.01 in the second study). AISRS is an interview-based scale for evaluating ADHD symptoms in adult patients, including hyperactivity/impulsivity and inattention subscales.
Key secondary efficacy endpoint data showed that in 2 studies, centanafadine also had a change in clinical overall impression-severity scale (CGI-S) from baseline to day 42 compared to placebo. Statistically significant improvement (p<0.05).
In a pooled analysis of 2 studies, the most common centanafadine side effects observed (approximately 5% incidence and more frequent than placebo) included decreased appetite, headache, nausea, dry mouth, upper respiratory tract infection, and diarrhea; no observation Side effects in patients with an incidence> 7%.
According to ADDA, about 5% (11 million) of adults in the United States have ADHD, a neurobehavioral disease that affects specific brain function and related behavioral regulation. These brain operations include important functions such as attention, attention, memory, motivation and effort, learning from mistakes, impulsivity, ADHD, organizational and social skills. There is no known cure for ADHD, and most people cannot get rid of the disease. About two thirds or more of children with ADHD still have symptoms and disease challenges in adulthood.