A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder

Daniel Y. Lin, Christopher J Kratochvil, Wen Xu, Ling Jin, Deborah N. D'Souza, William Kielbasa, Albert J. Allen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: The purpose of this study was to assess the efficacy and safety of edivoxetine (LY2216684), a selective norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: A fixed-dose, randomized, double-blind, 8 week study was conducted in patients 6-17 years of age, who were randomized by two strata: 1) Patients with prior stimulant use randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, or 0.3mg/kg/day arms in a 1:1:1:1 ratio; 2) Stimulant-naïve patients randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, 0.3mg/kg/day, or osmotic-release oral system methylphenidate (OROS MPH) (18-54mg/day based on body weight) arms in a 1:1:1:1:1 ratio. The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale (ADHD-RS) total score for edivoxetine 0.2mg/kg/day and 0.3mg/kg/day. Results: A total of 340 patients were randomized to placebo (n=78); edivoxetine 0.1mg/kg/day (n=76), 0.2mg/kg/day (n=75), or 0.3mg/kg/day (n=75); or OROS MPH (n=36). In the stimulant-naïve stratum, the positive control, OROS MPH, was significantly superior to placebo in mean ADHD-RS total score change at end-point (-19.46, p=0.015). The edivoxetine 0.2mg/kg/day and 0.3mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point (placebo -10.35; edivoxetine 0.2mg/kg/day -16.09, p<0.010; edivoxetine 0.3mg/kg/day -16.39, p<0.010) and Clinical Global Impressions-Improvement score (placebo 3.05; edivoxetine 0.1mg/kg/day 3.01, p=0.860; edivoxetine 0.2mg/kg/day 2.54, p=0.013; edivoxetine 0.3mg/kg/day 2.53, p=0.013). In the overall efficacy-analyses data set (n=270), the effect size estimates for edivoxetine doses 0.1mg/kg/day, 0.2mg/kg/day and 0.3mg/kg/day at the week 8 time point were 0.17, 0.51, and 0.54, respectively (for the stimulant-naïve stratum, the effect size estimate for OROS MPH was 0.69). Compared with placebo, edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse (p<0.050), and a smaller increase or slight decrease in weight. Conclusions: Edivoxetine at doses of 0.2mg/kg/day and 0.3mg/kg/day demonstrated efficacy in ADHD treatment, despite the presence of a sizeable placebo response. No unexpected adverse events were identified. Clinical Trial Registry identifier: NCT00922636

Original languageEnglish (US)
Pages (from-to)190-200
Number of pages11
JournalJournal of Child and Adolescent Psychopharmacology
Volume24
Issue number4
DOIs
StatePublished - May 1 2014

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alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol
Attention Deficit Disorder with Hyperactivity
Pediatrics
Placebos
Methylphenidate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder. / Lin, Daniel Y.; Kratochvil, Christopher J; Xu, Wen; Jin, Ling; D'Souza, Deborah N.; Kielbasa, William; Allen, Albert J.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 24, No. 4, 01.05.2014, p. 190-200.

Research output: Contribution to journalArticle

Lin, Daniel Y. ; Kratochvil, Christopher J ; Xu, Wen ; Jin, Ling ; D'Souza, Deborah N. ; Kielbasa, William ; Allen, Albert J. / A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder. In: Journal of Child and Adolescent Psychopharmacology. 2014 ; Vol. 24, No. 4. pp. 190-200.
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abstract = "Objective: The purpose of this study was to assess the efficacy and safety of edivoxetine (LY2216684), a selective norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: A fixed-dose, randomized, double-blind, 8 week study was conducted in patients 6-17 years of age, who were randomized by two strata: 1) Patients with prior stimulant use randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, or 0.3mg/kg/day arms in a 1:1:1:1 ratio; 2) Stimulant-na{\"i}ve patients randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, 0.3mg/kg/day, or osmotic-release oral system methylphenidate (OROS MPH) (18-54mg/day based on body weight) arms in a 1:1:1:1:1 ratio. The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale (ADHD-RS) total score for edivoxetine 0.2mg/kg/day and 0.3mg/kg/day. Results: A total of 340 patients were randomized to placebo (n=78); edivoxetine 0.1mg/kg/day (n=76), 0.2mg/kg/day (n=75), or 0.3mg/kg/day (n=75); or OROS MPH (n=36). In the stimulant-na{\"i}ve stratum, the positive control, OROS MPH, was significantly superior to placebo in mean ADHD-RS total score change at end-point (-19.46, p=0.015). The edivoxetine 0.2mg/kg/day and 0.3mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point (placebo -10.35; edivoxetine 0.2mg/kg/day -16.09, p<0.010; edivoxetine 0.3mg/kg/day -16.39, p<0.010) and Clinical Global Impressions-Improvement score (placebo 3.05; edivoxetine 0.1mg/kg/day 3.01, p=0.860; edivoxetine 0.2mg/kg/day 2.54, p=0.013; edivoxetine 0.3mg/kg/day 2.53, p=0.013). In the overall efficacy-analyses data set (n=270), the effect size estimates for edivoxetine doses 0.1mg/kg/day, 0.2mg/kg/day and 0.3mg/kg/day at the week 8 time point were 0.17, 0.51, and 0.54, respectively (for the stimulant-na{\"i}ve stratum, the effect size estimate for OROS MPH was 0.69). Compared with placebo, edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse (p<0.050), and a smaller increase or slight decrease in weight. Conclusions: Edivoxetine at doses of 0.2mg/kg/day and 0.3mg/kg/day demonstrated efficacy in ADHD treatment, despite the presence of a sizeable placebo response. No unexpected adverse events were identified. Clinical Trial Registry identifier: NCT00922636",
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T1 - A randomized trial of edivoxetine in pediatric patients with attention-deficit/hyperactivity disorder

AU - Lin, Daniel Y.

AU - Kratochvil, Christopher J

AU - Xu, Wen

AU - Jin, Ling

AU - D'Souza, Deborah N.

AU - Kielbasa, William

AU - Allen, Albert J.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Objective: The purpose of this study was to assess the efficacy and safety of edivoxetine (LY2216684), a selective norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: A fixed-dose, randomized, double-blind, 8 week study was conducted in patients 6-17 years of age, who were randomized by two strata: 1) Patients with prior stimulant use randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, or 0.3mg/kg/day arms in a 1:1:1:1 ratio; 2) Stimulant-naïve patients randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, 0.3mg/kg/day, or osmotic-release oral system methylphenidate (OROS MPH) (18-54mg/day based on body weight) arms in a 1:1:1:1:1 ratio. The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale (ADHD-RS) total score for edivoxetine 0.2mg/kg/day and 0.3mg/kg/day. Results: A total of 340 patients were randomized to placebo (n=78); edivoxetine 0.1mg/kg/day (n=76), 0.2mg/kg/day (n=75), or 0.3mg/kg/day (n=75); or OROS MPH (n=36). In the stimulant-naïve stratum, the positive control, OROS MPH, was significantly superior to placebo in mean ADHD-RS total score change at end-point (-19.46, p=0.015). The edivoxetine 0.2mg/kg/day and 0.3mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point (placebo -10.35; edivoxetine 0.2mg/kg/day -16.09, p<0.010; edivoxetine 0.3mg/kg/day -16.39, p<0.010) and Clinical Global Impressions-Improvement score (placebo 3.05; edivoxetine 0.1mg/kg/day 3.01, p=0.860; edivoxetine 0.2mg/kg/day 2.54, p=0.013; edivoxetine 0.3mg/kg/day 2.53, p=0.013). In the overall efficacy-analyses data set (n=270), the effect size estimates for edivoxetine doses 0.1mg/kg/day, 0.2mg/kg/day and 0.3mg/kg/day at the week 8 time point were 0.17, 0.51, and 0.54, respectively (for the stimulant-naïve stratum, the effect size estimate for OROS MPH was 0.69). Compared with placebo, edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse (p<0.050), and a smaller increase or slight decrease in weight. Conclusions: Edivoxetine at doses of 0.2mg/kg/day and 0.3mg/kg/day demonstrated efficacy in ADHD treatment, despite the presence of a sizeable placebo response. No unexpected adverse events were identified. Clinical Trial Registry identifier: NCT00922636

AB - Objective: The purpose of this study was to assess the efficacy and safety of edivoxetine (LY2216684), a selective norepinephrine reuptake inhibitor, in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: A fixed-dose, randomized, double-blind, 8 week study was conducted in patients 6-17 years of age, who were randomized by two strata: 1) Patients with prior stimulant use randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, or 0.3mg/kg/day arms in a 1:1:1:1 ratio; 2) Stimulant-naïve patients randomized to placebo, edivoxetine 0.1mg/kg/day, 0.2mg/kg/day, 0.3mg/kg/day, or osmotic-release oral system methylphenidate (OROS MPH) (18-54mg/day based on body weight) arms in a 1:1:1:1:1 ratio. The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale (ADHD-RS) total score for edivoxetine 0.2mg/kg/day and 0.3mg/kg/day. Results: A total of 340 patients were randomized to placebo (n=78); edivoxetine 0.1mg/kg/day (n=76), 0.2mg/kg/day (n=75), or 0.3mg/kg/day (n=75); or OROS MPH (n=36). In the stimulant-naïve stratum, the positive control, OROS MPH, was significantly superior to placebo in mean ADHD-RS total score change at end-point (-19.46, p=0.015). The edivoxetine 0.2mg/kg/day and 0.3mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point (placebo -10.35; edivoxetine 0.2mg/kg/day -16.09, p<0.010; edivoxetine 0.3mg/kg/day -16.39, p<0.010) and Clinical Global Impressions-Improvement score (placebo 3.05; edivoxetine 0.1mg/kg/day 3.01, p=0.860; edivoxetine 0.2mg/kg/day 2.54, p=0.013; edivoxetine 0.3mg/kg/day 2.53, p=0.013). In the overall efficacy-analyses data set (n=270), the effect size estimates for edivoxetine doses 0.1mg/kg/day, 0.2mg/kg/day and 0.3mg/kg/day at the week 8 time point were 0.17, 0.51, and 0.54, respectively (for the stimulant-naïve stratum, the effect size estimate for OROS MPH was 0.69). Compared with placebo, edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse (p<0.050), and a smaller increase or slight decrease in weight. Conclusions: Edivoxetine at doses of 0.2mg/kg/day and 0.3mg/kg/day demonstrated efficacy in ADHD treatment, despite the presence of a sizeable placebo response. No unexpected adverse events were identified. Clinical Trial Registry identifier: NCT00922636

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