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 (0.05–0.12 mg/kg/day – 6–12 years: 1–4 mg/day; 13–17 years: 1–7 mg/day), ATX (10–100 mg/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.