title: 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.affiliation: Child and Adolescent Mental Health Unit, University Hospital Mútua de Terrassa, UETD, Hospital Sant Joan de Deu, Barcelona, Spain. Electronic address: 32989ahz@comb.cat.
authors.forename: Amaia
authors.initials: A
authors.lastname: Hervas
authors.affiliation: Child and Adolescent Psychiatry, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Huss
authors.affiliation: The Gillberg Neuropsychiatry Centre at the Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Department of Child and Adolescent Psychiatry, Our Lady׳s Children׳s Hospital, Dublin, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: McNicholas
authors.affiliation: Center for Pediatric Excellence, Ottawa, ON, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: van Stralen
authors.affiliation: Shire, Eysins, Switzerland.
authors.forename: Sasha
authors.initials: S
authors.lastname: Sreckovic
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lyne
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Bloomfield
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
authors.affiliation: Shire, Wayne, PA, USA.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Robertson
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D003692:Delayed-Action Preparations / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011437:Propylamines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D011437:Propylamines; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride
keywords: Attention-deficit/hyperactivity disorder; Function; Guanfacine; Safety; Treatment efficacy