Executive Function Outcome of Treatment with Viloxazine Extended-Release Capsules in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Post-Hoc Analysis of Four Randomized Clinical Trials

Stephen V Faraone, Roberto Gomeni, Joseph T Hull, Gregory D Busse, Zare Melyan, Jonathan Rubin, Azmi Nasser, Stephen V Faraone, Roberto Gomeni, Joseph T Hull, Gregory D Busse, Zare Melyan, Jonathan Rubin, Azmi Nasser

Abstract

Aim: The aim of this study was to evaluate the effect of viloxazine extended-release capsules (viloxazine ER; Qelbree™) on executive function deficits (EFDs) in pediatric subjects (6-17 years of age) with attention-deficit/hyperactivity disorder (ADHD).

Methods: Data from four phase III placebo-controlled trials of 100-600 mg/day viloxazine ER (6-8 weeks of treatment) were used to evaluate the change from baseline (CFB) in the Conners 3rd Edition Parent Short Form-Executive Function (C3PS-EF) content scale T-score. Subjects were defined as EFD responders if they had C3PS-EF T-score > 70 at baseline and < 65 at end of study. ADHD symptoms were assessed with ADHD Rating Scale 5th Edition (ADHD-RS-5). Subjects were defined as ADHD symptom responders if they had a ≥ 50% reduction in CFB ADHD-RS-5 Total score at Week 6. The number needed to treat (NNT) and Cohen's d effect sizes were estimated for EFD and ADHD symptoms.

Results: A total of 1154 subjects were included in the analysis. Statistically significant improvements in EFDs were observed with viloxazine ER versus placebo (p = 0.0002). There were 52.5% of EFD or ADHD symptom responders in the viloxazine ER treatment group and 35.4% in the placebo group (p < 0.0001). The NNT was 5.8. The Cohen's d effect size for EFD and ADHD symptoms was 0.31.

Conclusion: Consistent with the efficacy of viloxazine ER demonstrated in pivotal trials, viloxazine ER significantly reduced EFDs in subjects with ADHD. Moreover, a substantial proportion of subjects treated with viloxazine ER had large improvements in EFDs, ADHD symptoms, or both.

Clinical trial registration numbers: NCT03247530, NCT03247517, NCT03247543, NCT03247556.

Conflict of interest statement

JTH, GDB, ZM, JR, and AN are employees of Supernus Pharmaceuticals, Inc. SVF received income, potential income, travel expenses, continuing education support and/or research support in the past year from Takeda, OnDosis, Tris, Otsuka, Arbor, Ironshore, Rhodes, Akili Interactive Labs, Enzymotec, Sunovion, Supernus, and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health; Oxford University Press: Schizophrenia: The Facts; and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. RG was a paid consultant to Ironshore Pharmaceuticals; Sunovion Pharmaceuticals; Supernus Pharmaceuticals; Teva; Biomedical Science Institutes; Nanomi BVs; Laboratorios Liconsa; Massachusetts General Hospital; UCB; Recordati Rare Diseases; Indivior, Tris Pharma; F. Hoffmann-La Roche.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Association between the changes in executive function and ADHD symptoms observed with viloxazine ER treatment. Positive scores denote improvement (scores on each axis are calculated by subtracting the EOS score from the baseline score). ADHD attention-deficit/hyperactivity disorder, ADHD-RS-5 ADHD Rating Scale 5th Edition, C3PS-EF Conners 3rd Edition Parent Short Form – Executive Function content scale, EOS end of study, viloxazine ER viloxazine extended-release capsules

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