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

• Published in: Clinical therapeutics Vol. 42; no. 8; pp. 1452 - 1466
• Main Authors: Nasser, Azmi, Liranso, Tesfaye, Adewole, Toyin, Fry, Nicholas, Hull, Joseph T., Chowdhry, Fatima, Busse, Gregory D., Cutler, Andrew J., Jones, Nandita Joshi, Findling, Robert L., Schwabe, Stefan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020; Elsevier Limited
• Subjects: Abdomen; ADHD; ADHD-RS-5; Age; Appetite; Appetite loss; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Child; Children; Clinical trials; Conners 3; Contraindications; Delayed-Action Preparations - administration & dosage; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; FDA approval; Female; Food; Guardians; Headache; Humans; Hyperactivity; Internal Medicine; Male; Medical Education; Mental disorders; Nausea; Pain; Safety; SPN-812; Statistical analysis; Stimulants; Suicide; Teenagers; Treatment Outcome; viloxazine; Viloxazine - administration & dosage; WFIRS; United States > US; ADHD; WFIRS; SPN-812; ADHD-RS-5; viloxazine; Conners 3
• DOI: 10.1016/j.clinthera.2020.05.021
• ISSN: 0149-2918; 1879-114X

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. 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. 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%. 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. •SPN-812 improved ADHD symptoms in children (ADHD-RS-5 and CGI-I scores vs placebo).•Higher 50% respondent rate per ADHD-RS-5 in SPN-812 treatment groups vs placebo.•Greater proportion of patients who improved (categorical CGI-I) vs placebo.•Parent-rated Conners 3-PS and WFIRS-P scales also indicate improvement.•SPN-812 (100-mg/day and 200-mg/day) was well tolerated with low discontinuation rates.