Qelbree (viloxazine extended-release capsules): Final Results of the Long-Term, Phase 3, Open-Label Extension Trial in Adults with ADHD

IntroductionViloxazine extended-release (ER) is an FDA-approved nonstimulant medication for ADHD in children (≥6 years) and adults. Approval in adults was based on a double-blind (DB) pivotal trial [NCT04016779] showing statistically significant efficacy on the Adult ADHD Investigator Symptom Rating Scale (AISRS; primary outcome). Here we report final results from the long-term, open-label extension (OLE) safety trial [NCT04143217] conducted as a following to the DB trial.MethodsUpon completing DB treatment, consenting subjects who enrolled in the OLE received viloxazine ER 200 mg/day, with flexible titration to an optimal maintenance dose (200-600 mg/day). Addition of a stimulant was permitted, at investigator’s discretion, following Week 12. OLE trial enrollment was temporarily closed at the outset of the COVID pandemic. Subjects completing the DB during this time were allowed delayed entry into the OLE upon requalification. Safety and efficacy measures were assessed relative to DB (or OLE re-entry) Baseline) at OLE Weeks 2, 4, and ~ every 8 weeks thereafter. The trial was planned for 3 years or until commercial availability of viloxazine ER.ResultsSubjects (N= 159; including 133 immediate- and 26 delayed-rollover) received viloxazine ER for 265 ± 254.9 days (mean ± SD). Nine subjects used adjunctive stimulant medication at some point after Week 12. Primary reasons for discontinuation included withdrawal of consent (25.6%), loss to follow up (17.7%), and adverse events (17.6%). Adverse events (experienced by 72.3%) were largely mild (26.4%) or moderate (40.3%) in severity and included (≥10%) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). Changes in clinical laboratory measures, vital signs, and ECG parameters were consistent with those observed in DB and product labeling. Suicidal ideation (wish to be dead) was reported by 3 subjects at a single visit each; no subject reported suicidal behavior. ADHD symptom (AISRS), executive function (BRIEF-A), global function (CGI), and quality of life (AAQOL) measures showed continued improvement in the OLE relative to that seen in DB. Baseline [mean ± SD)] AISRS Total, CGI-S, BRIEF-A GEC T-score and AAQOL ratings, respectively, were 37.9 ± 6.34), 4.6 ± 0.60, 70.4 ± 10.94 and 54.9 ± 14.96. All showed significant improvement (P