Qelbree® (viloxazine extended-release capsules): Final Results of the Long-Term, Phase 3, Open-Label Extension Trial in Adults With Attention-Deficit/Hyperactivity Disorder

This work was sponsored by Supernus Pharmaceuticals, Inc. Introduction: Viloxazine extended-release (ER) is an FDA-approved, nonstimulant medication for pediatric (≥6 years) and adult ADHD. In the pivotal phase 3 study leading to FDA-approval in adults, viloxazine ER showed significant improvement over placebo on the Adult ADHD Investigator Symptom Rating Scale (AISRS; primary outcome) by Week 2 through End of Study (EOS/Week 6); executive function (BRIEF A T-score) also significantly improved. Participants completing the double-blind (DB) study were eligible to enroll in the long-term, open-label extension (OLE) trial reported here. Methods: Participants received viloxazine ER 200 mg/day, with flexible titration (200-600 mg/day). Stimulant medication was allowed adjunctively (investigator discretion) following Week 12. Temporary trial closure at the outset of COVID pandemic prevented direct rollover to OLE for some participants; these were offered delayed entry following trial re-opening. Safety and efficacy (assessed relative to DB or trial re-entry Baseline) are reported. Results: Participants [Nf159 (including 26 delayed-rollover)] received viloxazine ER for mean (SD) 265 (254.9) days. Nine subjects initiated stimulants concomitantly at some point after Week 12. Adverse events led to discontinuation for 17.6% and included (≥10%) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). Respective ADHD (AISRS) and Executive function (BRIEF A GEC T-scores) scales measured 37.9 (6.34) and 70.4 (10.94) at Baseline and improved to 19.7 (12.16) and 58.3(16.19) by participants’ last study visit [CFB -18.2(11.54) and -12.9(13.48), respectively]. Conclusions: Participants receiving viloxazine ER in this long-term extension trial showed continued improvement in ADHD symptoms and executive function, with safety and tolerability similar to the DB trial.