Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Mar 16;51(2):43-64.

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  1 , Tesfaye Liranso  1 , Toyin Adewole  1 , Nicholas Fry  1 , Joseph T Hull  1 , Fatima Chowdhry  1 , Gregory D Busse  1 , Zare Melyan  1 , Andrew J Cutler  1 , Robert L Findling  1 , Stefan Schwabe  1
Affiliations
Randomized Controlled Trial

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 et al. Psychopharmacol Bull. .

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: The CFB at EOS ADHD-RS-5 Total score (least square [LS] means ± SE) for 400-mg/day, 600-mg/day SPN-812, and placebo was -18.3 ± 1.36, -16.7 ± 1.39, and -13.2 ± 1.38, respectively. The difference vs. placebo was statistically significant only for the 400-mg/day SPN-812 treatment group (600 mg/day: p = 0.0712; 400 mg/day: p = 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.

Keywords: adolescents; attention-deficit/hyperactivity disorder; viloxazine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study Design
Figure 2
Figure 2
Disposition of Subjects
Figure 3
Figure 3
Profile of the Change from Baseline in ADHD-RS-5 Total Score by Treatment Group and Week of Treatment
Figure 4
Figure 4
Proportion of CGI-I Responders by Treatment Group and Week of Treatment
See this image and copyright information in PMC

References

    1. Xu G, Strathearn L, Liu B, Yang B, Bao W. Twenty-Year Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among US Children and Adolescents, 1997–2016. JAMA Netw Open. 2018;1(4):e181471. - PMC - PubMed
    1. Klassen AF, Miller A, Fine S. Health-related quality of life in children and adolescents who have a diagnosis of attention-deficit/hyperactivity disorder. Pediatrics. 2004;114(5):e541–547. - PubMed
    1. Childress AC. Methylphenidate HCL for the treatment of ADHD in children and adolescents. Expert Opin Pharmacother. 2016;17(8):1171–1178. - PubMed
    1. Childress A, Tran C. Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder. Expert Opin Investig Drugs. 2016;25(4):463–474. - PubMed
    1. Biederman J, Mick E, Faraone SV. Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Am J Psychiatry. 2000;157(5):816–818. - PubMed

Publication types

LinkOut - more resources