A Phase 3 Placebo-Controlled Trial of Once-Daily 400-mg and 600-mg SPN-812 (Viloxazine Extended-Release) in Adolescents with ADHD.
Azmi Nasser, Tesfaye Liranso, Toyin Adewole, Nicholas Fry, Joseph T. Hull, Fatima Chowdhry, Gregory D. Busse, Zare Melyan, Andrew J. Cutler, Robert L. Findling, Stefan Schwabe
Abstract
Objectives: Three Phase 3 trials have demonstrated the efficacy and safety of SPN-812 in pediatric subjects with ADHD. Here, we report the results of a fourth trial. Methods: Eligible adolescent subjects (N = 297) were randomized to SPN-812 (400- or 600-mg/day) or placebo. The primary efficacy endpoint was change from baseline (CFB) at end of study (EOS) in the ADHD Rating Scale-5 (ADHD-RS-5) Total score. Statistical analyses included sequential testing for multiple treatment comparisons. Key secondary endpoints included: Clinical Global Impression-Improvement (CGI-I) score at EOS and CFB at EOS in the Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) Total average score. Results: = 0.0082). Neither dose could be considered superior to placebo due to the use of statistical method of sequential testing. Significant improvements were observed on a number of secondary endpoints. SPN-812 was well tolerated at both doses, with <5% discontinuation rate due to adverse events. Conclusions: Treatment with 400- but not 600-mg/day SPN-812 resulted in statistically significant improvement in the primary endpoint. The negative result seen in the 600-mg/day SPN-812 group was likely due to an unusually high placebo response. Safety data were consistent across all doses in the SPN-812 trials.