The Effect of Viloxazine Extended-Release Capsules on Functional Impairments Associated with Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents in Four Phase 3 Placebo-Controlled Trials

Azmi Nasser; Joseph T Hull; Tesfaye Liranso; Gregory D Busse; Zare Melyan; Ann C Childress; Frank A Lopez; Jonathan Rubin

doi:10.2147/NDT.S312011

The Effect of Viloxazine Extended-Release Capsules on Functional Impairments Associated with Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents in Four Phase 3 Placebo-Controlled Trials

Neuropsychiatr Dis Treat. 2021 Jun 3:17:1751-1762. doi: 10.2147/NDT.S312011. eCollection 2021.

Authors

Azmi Nasser¹, Joseph T Hull¹, Tesfaye Liranso², Gregory D Busse³, Zare Melyan³, Ann C Childress⁴, Frank A Lopez⁵, Jonathan Rubin⁶

Affiliations

¹ Department of Clinical Research, Supernus Pharmaceuticals, Inc., Rockville, MD, USA.
² Department of Biostatistics, Supernus Pharmaceuticals, Inc., Rockville, MD, USA.
³ Department of Medical Affairs, Supernus Pharmaceuticals, Inc., Rockville, MD, USA.
⁴ Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, NV, USA.
⁵ Children's Developmental Center, Winter Park, FL, USA.
⁶ Supernus Pharmaceuticals, Inc., Rockville, MD, USA.

Abstract

Purpose: The ADHD Rating Scale (ADHD-RS) assesses 18 symptoms of inattention and hyperactivity/impulsivity and has been used in many clinical trials to evaluate the treatment effect of drugs on ADHD. The fifth edition of this scale (ADHD-RS-5) also assesses the impact of inattention and hyperactivity/impulsivity symptoms on six domains of functional impairment (FI): family relationships, peer relationships, completing/returning homework, academic performance at school, controlling behavior at school, and self-esteem. Here, we report the effect of viloxazine extended-release capsules (viloxazine ER), a novel nonstimulant treatment for ADHD in children and adolescents (ages 6-17 years), on FI from a post hoc analysis of four randomized, double-blind, placebo-controlled Phase 3 clinical trials (N=1354).

Patients and methods: ADHD-RS-5 investigator ratings of ADHD symptoms and FIs were conducted at baseline and weekly post-baseline for 6-8 weeks in the four trials. Change from baseline (CFB) in ADHD-RS-5 FI scores (Total score [sum of 12 FI items] and Inattention and Hyperactivity/Impulsivity subscale scores [sum of 6 corresponding FI items]) and the 30% and 50% Responder Rates (ADHD-RS-5 FI Total score) were compared between viloxazine ER and placebo.

Results: The reduction (improvement) in ADHD-RS-5 FI scores (Total and subscale scores) and the percentage of responders (30% and 50%) at Week 6 were significantly greater in each viloxazine ER dose group vs placebo. In the 100-400 mg/day viloxazine ER groups, improvements were found as early as Week 1 (100-mg/day) or Week 2 (200-, 400-mg/day) of treatment. Analysis of individual items of ADHD-related FIs demonstrated that the effect of viloxazine ER was observed across all domains of impairment.

Conclusion: Significant improvements observed in ADHD-related FIs are consistent with the reduction in inattention and hyperactivity/impulsivity symptoms demonstrated in the viloxazine ER Phase 3 pediatric trials. Therefore, viloxazine ER provides clinically meaningful improvement of ADHD symptoms and functioning in children and adolescents with ADHD, starting as early as Week 1-2 of treatment.

Keywords: academic performance; behavior; impairment domains; self-esteem.

Grants and funding

The study was funded by Supernus Pharmaceuticals, Inc.