111 Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P301) Assessing Efficacy and Safety of Extended-Release Viloxazine in Children with ADHD.

STUDY OBJECTIVE: SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD. METHOD: Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score >/=28, a Clinical Global Impression-Severity score >/=4, and be free of ADHD medication >/=1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale. RESULTS: Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p /=5%) treatment-related AEs reported were somnolence, decreased appetite, and headache. CONCLUSIONS: In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were