A post hoc analysis of the effect of viloxazine extended-release capsules on learning and school problems in children and adolescents with attention-deficit/hyperactivity disorder

Abstract

Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms vs. placebo was reported in a series of pediatric clinical trials of viloxazine extended-release capsules (viloxazine ER; Qelbree™). This post hoc analysis of those studies evaluated the effect of viloxazine ER on learning and school problems (LSPs). We used data from four Phase 3 placebo-controlled trials of 100–600 mg/day viloxazine ER (N = 1354; 6–17 years of age). LSPs were evaluated using the School domain of the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P-S) and the Learning Problems content scale of the Conners 3rd Edition-Parent Short Form (C3PS-LP) at baseline and end of study (≥ Week 6). ADHD symptoms were assessed weekly using the ADHD Rating Scale 5th Edition. The analyses were performed using the general linear mixed model with participant as a random effect. The responder analyses were performed using the Chi-square test. Viloxazine ER demonstrated significantly greater improvements in WFIRS-P-S (p < 0.0001) and C3PS-LP (p = 0.0113) scores vs. placebo. The response rate for the WFIRS-P-S was significantly greater for viloxazine ER vs. placebo (p = 0.001), and the number needed to treat (NNT) was 10.3 (effect size 0.7). Conversely, response rates for C3PS-LP did not differ between groups (p = 0.9069). In addition to ADHD symptoms improvement demonstrated in previous studies, viloxazine ER significantly reduced LSPs in pediatric subjects with ADHD. The responder analyses and NNT estimates indicate that a substantial number of children and adolescents with ADHD treated with viloxazine ER improved in clinically assessed LSPs.

Response of peer relations and social activities to treatment with viloxazine extended‐release capsules (Qelbree®): A post hoc analysis of four randomized clinical trials of children and adolescents with attention‐deficit/hyperactivity disorder

“…The methods outlined here have been described previously (Faraone, Gomeni, Hull, Busse, Melyan, Rubin, et al., 2021 ).…”

“…A series of Phase III clinical trials have been completed for viloxazine ER demonstrating its safety and efficacy in reducing the symptoms of ADHD in children and adolescents (Nasser et al., 2020 ; Nasser, Liranso, Adewole, Fry, et al., 2021a ; Liranso, Adewole, Fry, Hull, Busse, et al., 2021 ). Moreover, a recent study in pediatric ADHD subjects demonstrated that the effect of viloxazine ER treatment on ADHD‐related functional impairment provides clinically meaningful improvements (Faraone, Gomeni, Hull, Busse, Melyan, Rubin, et al., 2021 ; Nasser, Liranso, Busse, et al., 2021 ).…”

Viloxazine: A New Non-Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD)

“…The phase III trials data report suggest a well-tolerated clinical profile of viloxazine with a low incidence and mild severity of adverse effects [14,15], including a small number of cardiovascular abnormalities [16] and liver enzyme elevations [2,17]. Viloxazine was reported effective in reducing ADHD symptoms in children such as inattention and hyperactivity/impulsivity [3,18], significantly reduces the impairment of peer relations and social activities in children and adolescents with ADHD [19] as well as school learning problems [20]. The trial results demonstrated the efficacy of viloxazine for ADHD symptoms, which can manifest as early as week 1 of treatment, along with a safe and well-tolerated clinical profile.…”

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder

“…The therapeutic effects of this novel nonstimulant medication are thought to be owing to its action as a norepinephrine reuptake inhibitor; however, contemporary preclinical studies indicate that it may also act on serotonergic signaling in the brain, though the translational effect in humans remains to be fully elucidated [25,26]. In three phase III, randomized, placebo-controlled clinical trials in children [27,28] and adolescents [29], viloxazine ER statistically significantly and clinically meaningfully [30,31] reduced ADHD symptoms and improved functional impairment [32], executive function [44], and learning/school performance [33]. Additionally, viloxazine ER showed no pharmacokinetic interactions with ADHD stimulant treatments (e.g., lisdexamfetamine and methylphenidate) [34,35] nor was the pharmacokinetics of viloxazine ER meaningfully affected by strong cytochrome P450 (CYP) 2D6 inhibitors such as paroxetine or the presence of CYP2D6 genetic polymorphisms [36,37].…”