The experimental nonstimulant medication viloxazine extended-release, known as SPN-812, reduced symptoms of attention-deficit/hyperactivity disorder (ADHD) as soon as 1 week after dosing and was well tolerated in a randomized, placebo-controlled phase 3 study that included more than 400 children.
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In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interviews.
Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.
The findings were published online July 25 in Clinical Therapeutics.
Novel modulating agent
Viloxazine extended-release is a novel multimodal serotonergic and noradrenergic modulating agent with activity at serotonin receptors and the norepinephrine transporter.
About two-thirds were boys.
All participants had an ADHD-Rating Scale–5 (ADHD-RS-5) score of at least 28 and a Clinical Global Impression–Severity score of at least 4. None had taken ADHD medication for at least 1 week prior to randomization.
The intent-to-treat population included 460 children. Of these, 155 were randomly assigned to receive placebo, 147 to receive viloxazine 100 mg, and 158 to receive viloxazine 200 mg.
The primary efficacy endpoint was change from baseline in ADHD-RS-5 total score at week 6. Score changes for both the 100-mg (P = .0004) and the 200-mg (P < .0001) viloxazine groups met statistical significance compared with the placebo group.
Change from baseline in both the ADHD-RS-5 inattention and hyperactivity/impulsivity subscale scores was also significantly reduced in the 100-mg (P = .0006 and .0026, respectively) and 200-mg (P < .0001 and P < .0001, respectively) treatment groups compared with the placebo group.
Improvements occurred after 1 week of treatment and were maintained throughout the 6-week trial, “indicating an early and sustained effect,” the investigators wrote.
FDA target action date
The Clinical Global Impression–Improvement (CGI-I) score at 6 weeks was significantly improved in those receiving 100 mg (P = .0020) and 200 mg (P < .0001) of the active treatment compared with placebo.
The CGI-I responder rate, the percentage of children with a CGI-I score of 1 (very much improved) or 2 (much improved), was significantly higher at 6 weeks with viloxazine 100 mg and 200 mg vs. placebo (45% and 51% vs. 30%, respectively; P = .0065 and P = .0002).
These standard investigator-rated assessments were supported by two parent self-rated assessments: the Conners 3–Parent Short Form and the Weiss Functional Impairment Rating Scale–Parent Form.
Parents noted improvement not only in their children’s ADHD symptoms but also in ADHD-associated learning problems, executive functioning, defiance/aggression, peer relations, and functioning in different settings.
At both doses, once-daily viloxazine was generally well tolerated, with a low rate of discontinuation because of adverse events (<5%). Most adverse events were characterized as mild or moderate in severity and included somnolence (8.9%), decreased appetite (6.0%), and headache (5.4%).
On the basis of results of this study and others, the Food and Drug Administration accepted the company’s new drug application for viloxazine extended-release for ADHD in children and adolescents. The application has a target action date of Nov. 8, 2020.