Background: Although stimulants are commonly used for attention-deficit/hyperactivity disorder (ADHD), 10–30% of patients have an inadequate response, adverse events, or comorbidities preventing use. There is a need for safe, effective nonstimulant options. Extended-release viloxazine (SPN-812) is a nonstimulant in development for treatment of ADHD in children and adolescents. SPN-812 is a structurally distinct, bicyclic norepinephrine reuptake inhibitor with selective serotonergic activity. Phase 2 studies demonstrated efficacy and safety of SPN-812 in children.
Methods: Four ongoing Phase 3 randomized, double-blind, placebo-controlled studies are investigating the efficacy and safety of once-daily SPN-812 for ADHD in children (ages 6–11; 100–400mg) and adolescents (ages 12–17; 200–600mg). Eligible subjects have minimum baseline scores of ≥28 on the ADHD Rating Scale-5 (ADHD-RS-5) and ≥4 on the Clinical Global Impression-Severity scale. These studies will randomize ~1200 children/adolescents, with ~800 subjects receiving SPN-812 over 1–3-week titration and 5-week maintenance periods. The primary endpoint is mean change from baseline to end of study in the ADHD-RS-5 total score, with additional secondary endpoints. Safety assessments include adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and the Columbia-Suicide Severity Rating Scale. Phase 3 completers may enter an open-label extension (OLE).
Results: As of August 2018, enrollment in 1 child study is complete; the other 3 studies are at ~89%. Rollover into the OLE is ~90%.
Summary: The safety and efficacy of SPN-812 are being investigated in Phase 3 randomized, placebo-controlled studies for treatment of ADHD in children and adolescents.