Efficacy and safety of extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial.

Abstract

Guanfacine extended-release (GXR), a selective α2A-adrenergic agonist, is a non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD). This study assessed the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo. Patients (6-17 years) were randomized at baseline to dose-optimized GXR (0.05-0.12mg/kg/day - 6-12 years: 1-4mg/day; 13-17 years: 1-7mg/day), ATX (10-100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure was change from baseline in ADHD Rating Scale version IV (ADHD-RS-IV). Key secondary measures were Clinical Global Impression-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P; learning and school, and family domains). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs. A total of 272 (80.5%) patients from Europe, the USA and Canada completed the study. Significant differences were observed in least squares mean change from baseline in ADHD-RS-IV total score (placebo-adjusted differences) (GXR: [-8.9, p<0.001]; ATX: [-3.8, p<0.05]), the difference from placebo in the percentage of patients showing improvement (1 ['very much improved'] or 2 ['much improved']) for CGI-I (GXR: [23.7, p<0.001]; ATX: [12.1, p<0.05]), WFIRS-P learning and school domain (GXR: [-0.22, p<0.01]; ATX: [-0.16, p<0.05]) and WFIRS-P family domain (GXR: [-0.21, p<0.01]; ATX: [-0.09, p=0.242]). Most common TEAEs for GXR were somnolence, headache and fatigue; 70.1% of GXR subjects reported mild-to-moderate TEAEs. GXR was effective and well tolerated in children and adolescents with ADHD.

• Authors: Amaia Hervas, Michael Huss, Mats Johnson, Fiona McNicholas, Judy van Stralen, Sasha Sreckovic, Andrew Lyne, Ralph Bloomfield, Vanja Sikirica, Brigitte Robertson
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 24 Issue 12 Pg. 1861-72 (Dec 2014) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 25453486 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Chemical References

• Adrenergic Uptake Inhibitors
• Adrenergic alpha-2 Receptor Agonists
• Delayed-Action Preparations
• Propylamines
• Guanfacine
• Atomoxetine Hydrochloride

Topics

• Adolescent
• Adrenergic Uptake Inhibitors (therapeutic use)
• Adrenergic alpha-2 Receptor Agonists (administration & dosage, adverse effects, therapeutic use)
• Atomoxetine Hydrochloride
• Attention Deficit Disorder with Hyperactivity (drug therapy)
• Child
• Delayed-Action Preparations (adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Guanfacine (administration & dosage, adverse effects, therapeutic use)
• Humans
• Male
• Propylamines (therapeutic use)
• Psychiatric Status Rating Scales