Viloxazine ER (Qelbree®) Administered with Psychostimulants in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Topline Results of a Phase IV Safety Trial

This work was sponsored by Supernus Pharmaceuticals, Inc. Introduction: Approximately 10%-30% of individuals with ADHD experience inadequate response or have difficulty tolerating stimulant medications. Viloxazine extended-release (ER) is a nonstimulant, FDA-approved for pediatric (≥6 years) and adult ADHD. We report results of a phase IV, open-label safety study evaluating viloxazine ER administered with psychostimulants in pediatric (6-17 years) ADHD; morning vs. evening administration of viloxazine ER was also evaluated. Methods: Following screening period of ≤ 4 weeks, subjects who continued to experience inadequate efficacy (ADHD-RS-5 ≥24; CGI-S ≥3) to psychostimulant treatment (methylphenidate or amphetamine) received viloxazine ER, flexibly dosed (100-600 mg) each morning during Weeks 1-4 and evening during Weeks 5-8. Safety (primary outcome) and efficacy were evaluated relative to Baseline and for AM vs. PM viloxazine ER dosing. Results: Fifty-six subjects received viloxazine ER; 85.7% of these completed. Commonly reported adverse events (AEs) were headache (17.9%), decreased appetite (12.5%), and upper respiratory tract infection (10.7%); AEs led to discontinuation for 3.6%. Respective mean (SD) ADHD-RS-5 and CGI-S scores were Baseline (n=56): 37.2 (8.35) and 4.4 (0.56), Week 4 (n=54): 24.0 (11.66) and 3.6 (0.92) and Week 8 (n=48): 19.4 (12.08) and 3.1 (1.08), representing significant improvements from Baseline of -13.5 (9.7) and - 0.9 (0.92), and -18.2 (9.99) and -1.4 (1.10), respectively [All P.0001]. Results were also significantly different for AM vs. PM dosing [P.0005]. Conclusions: Viloxazine ER showed acceptable safety and tolerability when administered with stimulant medications. ADHD symptoms improved following viloxazine ER addition to stimulants, with both AM and PM dosing appearing safe and effective.