Once-Daily SPN-812 200 and 400 mg in the treatment of ADHD in School-aged Children: A Phase III Randomized, Controlled Trial

Abstract Purpose SPN-812 (viloxazine extended-release) is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase III study evaluated the efficacy and tolerability of SPN-812 200 and 400 mg once daily in children 6–11 years of age with ADHD. Methods Patients were randomly assigned to receive SPN-812 200 mg, SPN-812 400 mg, or placebo, once daily for 8 weeks (including ≤3 weeks titration period). The primary efficacy endpoint was the change from baseline (CFB) in ADHD Rating Scale (RS)-5 Total score at end of study (EOS). Key secondary endpoints included Clinical Global Impression–Improvement (CGI-I) score at EOS, CFB in Conners 3–Parent Short Form (PS) composite T-score at EOS, and CFB in Weiss Functional Impairment Rating Scale–Parent (WFIRS-P) Total average score at EOS. Findings A total of 313 patients were enrolled, with 301 in the intent-to-treat population (194 boys, 107 girls; mean age [SD], 8.4 [1.7] years). At EOS, the CFBs in ADHD-RS-5 Total score and CGI-I score were significantly improved with both 200- and 400-mg/d SPN-812 versus placebo (ADHD-RS-5, P = 0.0038 and 0.0063, respectively; CGI-I, P = 0.0028 and 0.0099). At EOS, the CFB in Conners 3-PS composite T-score was significantly improved with 200- (P = 0.0064), but not 400-mg/d (P = 0.0917), SPN-812 compared to placebo. No significant difference between the groups was found in WFIRS-P Total average score. The rate of discontinuations due to adverse events in both SPN-812 treatment groups combined was Implications SPN-812 200 and 400 mg once daily was associated with improvements in ADHD symptoms in school-aged children and was generally well tolerated. ClinicalTrials.gov identifier: NCT03247543. (Clin Ther. 2021; 43:XXX–XXX) © 2021 Elsevier Inc.