PMID- 32723670 OWN - NLM STAT- MEDLINE DCOM- 20210127 LR - 20210127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 42 IP - 8 DP - 2020 Aug TI - A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children. PG - 1452-1466 LID - S0149-2918(20)30283-6 [pii] LID - 10.1016/j.clinthera.2020.05.021 [doi] AB - PURPOSE: The limitations of current US Food and Drug Administration (FDA)-approved medications for the treatment of attention-deficit/hyperactivity disorder (ADHD) set the need for the development of novel, effective, and tolerable medications to treat this disorder. The purpose of this study was to evaluate whether treatment with SPN-812 (viloxazine extended-release) significantly reduces symptoms of ADHD in children. METHODS: This study was a randomized, double-blind, placebo-controlled 6-week trial to assess the efficacy and safety of once-daily 100- and 200-mg SPN-812 in the treatment of ADHD in male and female children 6-11 years of age. Inclusion criteria required subjects to have a confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, ADHD diagnosis, an ADHD-Rating Scale-5 (ADHD-RS-5) score >/=28, a Clinical Global Impression-Severity score >/=4, and for subjects to be free of ADHD medication >/=1 week before randomization. The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 Total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS and CFB at EOS in the Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) Total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical examinations, ECGs, and the Columbia-Suicide Severity Rating Scale. The primary efficacy endpoint was analyzed by using a mixed model for repeated measures; all secondary measures were analyzed by using an ANCOVA model. RESULTS: A total of 477 subjects were randomized to treatment (intent-to-treat population, n = 460). The majority of subjects were male (63%) and either White (51.3%) or African American (43.7%). The demographic and baseline characteristics between the groups were similar. Statistically significant improvements in ADHD-RS-5 Total score were observed in both the 100- and 200-mg/day SPN-812 treatment groups compared to placebo at week 1 of treatment (P = 0.0004 and P = 0.0244, respectively), which was maintained through EOS (P = 0.0004 and P < 0.0001). Significant improvements were also observed at EOS in the CGI-I scale (P = 0.0020 and P < 0.0001), Conners 3-PS Composite T-score (P = 0.0003 and P = 0.0002), and WFIRS-P Total average score (P = 0.0019 and P = 0.0002) versus placebo. Treatment-related AEs reported in >/=5% of subjects included somnolence, decreased appetite, and headache. The discontinuation rate due to AEs was <5%. IMPLICATIONS: SPN-812 significantly reduced ADHD symptoms in children and was well tolerated. SPN-812 may prove to be an effective treatment for children with ADHD. ClinicalTrials.gov identifier: NCT03247530. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Nasser, Azmi AU - Nasser A AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. Electronic address: anasser@supernus.com. FAU - Liranso, Tesfaye AU - Liranso T AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Adewole, Toyin AU - Adewole T AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Fry, Nicholas AU - Fry N AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Hull, Joseph T AU - Hull JT AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Chowdhry, Fatima AU - Chowdhry F AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Busse, Gregory D AU - Busse GD AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. FAU - Cutler, Andrew J AU - Cutler AJ AD - SUNY Upstate Medical University, and Neuroscience Education Institute, Lakewood Ranch, FL, USA. FAU - Jones, Nandita Joshi AU - Jones NJ AD - CNS Healthcare, Jacksonville, FL, USA. FAU - Findling, Robert L AU - Findling RL AD - Virginia Commonwealth University School of Medicine, Richmond, VA, USA. FAU - Schwabe, Stefan AU - Schwabe S AD - Supernus Pharmaceuticals, Inc, Rockville, MD, USA. LA - eng SI - ClinicalTrials.gov/NCT03247530 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200725 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Delayed-Action Preparations) RN - 5I5Y2789ZF (Viloxazine) SB - IM MH - Attention Deficit Disorder with Hyperactivity/*drug therapy MH - Child MH - Delayed-Action Preparations/*administration & dosage MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Male MH - Treatment Outcome MH - Viloxazine/*administration & dosage OTO - NOTNLM OT - ADHD OT - ADHD-RS-5 OT - Conners 3 OT - SPN-812 OT - WFIRS OT - viloxazine EDAT- 2020/07/30 06:00 MHDA- 2021/01/28 06:00 CRDT- 2020/07/30 06:00 PHST- 2020/04/15 00:00 [received] PHST- 2020/05/21 00:00 [revised] PHST- 2020/05/29 00:00 [accepted] PHST- 2020/07/30 06:00 [pubmed] PHST- 2021/01/28 06:00 [medline] PHST- 2020/07/30 06:00 [entrez] AID - S0149-2918(20)30283-6 [pii] AID - 10.1016/j.clinthera.2020.05.021 [doi] PST - ppublish SO - Clin Ther. 2020 Aug;42(8):1452-1466. doi: 10.1016/j.clinthera.2020.05.021. Epub 2020 Jul 25.