Clinical Outcomes from an Open-Label Study of Edivoxetine Use in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

Abstract

This study provides preliminary evidence to suggest that edivoxetine at doses ≤0.3 mg/kg/day is safe and may improve ADHD symptoms in pediatric patients. These results require confirmation in larger, double-blind, placebo-controlled trials.

A Randomized Trial of Edivoxetine in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

“…A dosing paradigm that provides better separation across treatment groups may be beneficial in further understanding the exposure -efficacy -safety relationship of edivoxetine. The safety profile of edivoxetine was similar to that seen in a previous study of edivoxetine ( Jin et al 2013), as well as to that seen in studies of drugs with a similar mechanism of action (i.e., inhibition or norepinephrine reuptake) such as atomoxetine, in pediatric patients with ADHD (Michelson et al 2001). There were no significant differences between treatment arms in the number of patients who discontinued because of an adverse event, and there were no deaths or serious adverse events reported in this study.…”

“…The dose levels of edivoxetine selected for this study were based on results obtained from a previous open-label study investigating the safety, effectiveness, PK, and PD of edivoxetine (Kielbasa et al 2012;Jin et al 2013). The actual amount of edivoxetine (in milligrams) administered to patients in this study was based on an approximation of the median body weight within the range and the fixed-dose treatment arms to which they were randomized.…”

“…In a previous open-label study of edivoxetine at targeted doses of 0.05 mg/kg/day, 0.1 mg/ kg/day, 0.2 mg/kg/day, and 0.3 mg/kg/day in pediatric patients with ADHD, the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHD-RS-IV-Parent:Inv) total score, inattention and hyperactivity/ impulsivity subscores, and Clinical Global Impressions-AttentionDeficit/Hyperactivity Disorder-Severity (CGI-ADHD-S) scores were statistically significantly improved at end-point compared with baseline ( Jin et al 2013). From that same study, the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of edivoxetine were also examined using measurement of the intraneuronal metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a functional measure of norepinephrine transporter (NET) activity (Kielbasa et al 2012).…”

Pharmacodynamics of norepinephrine reuptake inhibition: Modeling the peripheral and central effects of atomoxetine, duloxetine, and edivoxetine on the biomarker 3,4‐dihydroxyphenylglycol in humans

“…Atomoxetine given to children with ADHD caused changes in their urine DHPG‐to‐NE ratio, and in healthy subjects, it decreased plasma, CSF, and urine concentrations of DHPG . Edivoxetine is also a selective NET inhibitor that was evaluated as a monotherapy treatment for children and adolescents with ADHD and in adults with MDD . Phase 3 trials of edivoxetine as adjunctive treatment for patients with MDD did not meet the primary study objective for efficacy .…”

New Research

“…Stimulantprior patients were randomized to placebo or one of the three fixed-dose arms of edivoxetine. Of note, the fixed-dose levels of edivoxetine were chosen based on results of prior pK studies (Jin et al, 2013;Kielbasa et al, 2012). The OROS MPH arm served as a positive control for study validation, and not as a direct comparison to edivoxetine.…”