Extended-release viloxazine for ADHD in kids scores high in phase III trial

Jairia Dela Cruz
10 Mar 2021

The investigational attention-deficit/hyperactivity disorder (ADHD) medication viloxazine extended-release, known as SPN-812, rapidly reduces symptoms in school-aged children with a tolerable safety profile, as shown in the results of a phase III trial.

“The consistent improvements in ADHD symptoms, as measured using two clinical assessment scales (ADHD Rating Scale [RS]-5 and Clinical Global Impression–Improvement [CGI-I]), with SPN-812 compared to placebo start early after the initiation of treatment. This finding is supported by higher rates of response and parent-rated improvements in ADHD symptoms and function,” according to the investigators.

A total of 313 children were enrolled and randomized to receive SPN-812 at 200 mg (n=107) or 400 mg (102) or placebo (n=104) once daily for 8 weeks (including ≤3 weeks titration period). The intent-to-treat population comprised 301 children (mean age, 8.4 years; 64.5 percent boys), while that of safety involved 310. Baseline demographic and clinical characteristics were similar across the treatment groups.

Week-8 data showed that compared with placebo, both SPN-812 doses produced clinically meaningful changes in ADHD-RS-5 total score (p=0.0038 and p=0.0063, respectively) and CGI-I score (p=0.0028 and p=0.0099, respectively).  [Clin Ther 2021;doi:10.1016/j.clinthera.2021.01.027]

“The improvement in ADHD-RS-5 total score versus placebo was apparent at week 1 in the 200-mg group, and at week 5 in the 400-mg group (despite up to 3 weeks of titration),” the investigators noted.

Meanwhile, the favourable effects on Conners 3–Parent Short Form (PS) composite T-score were significant in the 200-mg group (p=0.0064) but not in the higher-dose group (p=0.0917). There were no important between-group differences found in Weiss Functional Impairment Rating Scale–Parent (WFIRS-P) total average score.

SPN-812 was well tolerated, with the combined rate of discontinuations due to adverse events (AEs) low at <5 percent.

“These data, taken together with a low overall incidence of AEs and no clinically relevant trends observed on clinical laboratory tests, vital sign measurements, or ECG, indicate that SPN-812 may be an effective and overall well-tolerated treatment option for ADHD in children aged 6–11 years,” according to the investigators.

“The minimal effects on blood pressure and heart rate, in particular, are a potential differentiator from currently available ADHD medications,” they added.

Other phase III trials in younger children and in adolescents also demonstrated the efficacy of SPN-812 (100, 200, and 400 mg/d) in reducing the symptoms of ADHD while being well tolerated. In a posthoc analysis of data from these trials, the number needed to treat in children with ADHD (6–11 years of age) was 6–7, consistent with reports from trials of other nonstimulant drugs. [Clin Ther 2020;42:1452-1466; J Am Acad Child Adolesc Psychiatry 2014;53:153-157/174-187]

“One challenge associated with the treatment of ADHD in children is a high rate of comorbid disorders leading to modest improvements in function observed in clinical practice, and even in noncomorbid ADHD, optimal functioning occurs in only [about] one in four children. Additionally, medications may improve some but not all aspects of cognitive function, with many patients experiencing residual disabilities in several areas, including executive function, emotional self-regulation, and academic performance,” the investigators acknowledged. [Patient 2015;8:269-281; BMC Med 2011;9:72; Paediatr Drugs 2015;17 459-477]

Also, current formulations of nonstimulant ADHD medications (solid tablets or capsules) cannot be sprinkled over food and may bar their use in children having difficulty swallowing or who prefer not to take pills (eg, those with autism, sensory processing disorder, or other developmental disabilities). [CNS Spectr 2017;22:463-474]

Considering the complexity of ADHD and the potential tolerability-related limitations of currently available FDA-approved medications, new effective treatment options with diminished risk, such as extended-release viloxazine, could improve the management of this common neurodevelopmental disorder, the investigators said.

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