Results from a pivotal phase 2/3 study of the investigational drug candidate dasotraline (Sunovion Pharmaceuticals) in children 6 to 12 years of age with attention-deficit/hyperactivity disorder (ADHD) have shown a statistically significant improvement in the 4-mg per day arm compared with placebo. The 2-mg per day dosage did not demonstrate a statistically significant difference versus placebo.
Pending successful completion of ongoing studies and discussions with the FDA, Sunovion intends to submit a new drug application for dasotraline for the treatment of ADHD in children and adults later this year.
Dasotraline is a dopamine and norepinephrine reuptake inhibitor (DNRI). Its extended half-life (47 to 77 hours) supports the potential for a continuous therapeutic effect during the 24-hour dosing interval at steady state, according to Sunovion. Dasotraline is currently in development for ADHD in adults and children and for binge-eating disorder (BED) in adults. It has not been approved by the FDA for the treatment of ADHD, BED, or any other disorders.
The six-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial compared dasotraline with placebo in children 6 to 12 years of age with a primary diagnosis of ADHD, according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5); an ADHD Rating Scale [RS]-IV Home Version (HV) score of 28; and a Clinical Global Impression–Severity of Illness Scale (CGI-S) score of 4 at baseline.
A total of 342 patients were randomly assigned to receive dasotraline 2 mg per day (n = 111), dasotraline 4 mg per day (n = 115), or placebo (n = 116) once daily. Patients in the 4-mg per day arm started at the 2-mg per day dosage for the first week of the study and were increased to 4 mg per day at week 2. The primary efficacy endpoint was the change from baseline at week 6 in ADHD symptoms, as measured by the ADHD RS-IV total score. Secondary efficacy endpoints included the change from baseline in ADHD symptoms, as measured by the ADHD RS-IV HV score at weeks 1 to 5 (and subscales at weeks 1 to 6); the CGI-S score at weeks 1 to 6; and the percentage of responders (defined as a 30% reduction in the ADHD RS-IV HV total score at weeks 1 to 6).
Children treated with dasotraline 4 mg per day showed a statistically significant improvement in ADHD symptoms compared with placebo, as measured by the ADHD RS-IV HV total score (least squares mean change from baseline at week 6: –17.53 versus –11.36, respectively; P < 0.001). This statistically significant improvement compared with placebo was maintained each week through week 6. Improvements in CGI-S scores were also statistically significant in the 4-mg per day arm compared with the placebo arm. The 2-mg per day dosage did not demonstrate a statistically significant difference from placebo in the ADHD RS-IV total scores and did not statistically separate from placebo in the CGI-S scores.
Both dasotraline arms were generally well tolerated. The most common treatment-related adverse events included insomnia, decreased appetite, and decreased weight.
Source: Sunovion Pharmaceuticals; January 14, 2017.