9 Phase 3 Randomized, Double-blind, Placebo-Controlled Studies Evaluating Efficacy and Safety of Extended-Release Viloxazine for Pediatric ADHD

Abstract

Study Objectives

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. Thus, there is a need for safe, effective nonstimulant options. Extended-release viloxazine (SPN-812), a nonstimulant, is currently in development for the treatment of ADHD in children and adolescents. SPN-812 is a structurally distinct, bicyclic norepinephrine reuptake inhibitor with selective serotonergic activity. Results of the Phase 2 program demonstrated efficacy (improved mean ADHD Rating Scale-IV total score) and safety of SPN-812 in children (6–12 years), as well as an onset of action within 1–2 weeks.

Method

Four ongoing Phase 3 randomized, double-blind, placebo-controlled, outpatient, US 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). Two studies are enrolling children and two are enrolling adolescents. Eligible subjects are required to have minimum baseline scores of ≥28 for ADHD-RS-5 and ≥4 for Clinical Global Impression-Severity scale (CGI-S). These studies will randomize ∼1200 subjects, with ∼800 subjects receiving SPN-812 over a 1–3-week titration and 5-week maintenance period. The primary endpoint in all studies is mean change from baseline to end of study (EOS) in ADHD-RS-5 total score for SPN-812 vs. placebo. Secondary endpoints include change from baseline to EOS in 30% responder rate (% change: ADHD RS 5); Hyperactivity/Impulsivity and Inattention ADHD-RS-5 subscale scores; Conners 3 Rating Scale (parent and self-report); CGI-S/CGI-I (Improvement); Weiss Functional Impairment Rating Scale (parent report); Parenting Stress Index (children); and Stress Index for Parents of Adolescents (adolescents) after 6–8 weeks of treatment. Safety is assessed via adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and the Columbia-Suicide Severity Rating Scale. Phase 3 completers are offered the option of enrolling in an open-label extension study (OLE; up to 3 years) with a starting dose of 100/200mg (children/adolescents). Data will be summarized with descriptive statistics and analyzed using appropriate statistical methods.

Results

As of August 2018, enrollment in 1 child study is complete, and the other 3 trials are at ∼89%; rollover into the OLE is ∼90%.

Conclusions

There is an unmet need for nonstimulant ADHD treatment for children and adolescents that is effective, long-acting, and well tolerated. SPN-812 is being investigated in four Phase 3 randomized, placebo-controlled studies for the treatment of children and adolescents with ADHD, based on demonstrated efficacy and safety in the Phase 2 program.

This study is an encore of a poster presentation at the 2018 Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP).

Funding Acknowledgements: Supernus Pharmaceuticals, Inc.