EPA-0685 – Guanfacine XR (GXR) for children and adolescents with attention-deficit/hyperactivity disorder (ADHD): phase 3, randomized, double-blind, multicenter, placebo- and active-reference study

Abstract

Introduction GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children). Objectives To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD. Aims To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490). Methods Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Results Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe. Conclusions GXR was effective and well tolerated in children and adolescents with ADHD. GXR ATX Placebo-adjusted difference in LS mean change from baseline in ADHD-RS-IV total score (95% Cl, p-value; effect size) −8.9 (−11.9, −5.8, p −3.8 (−6.8, −0.7, p Difference in improvement from placebo for CGI-I (95% Cl, p-value) 23.7% (11.1, 36.4; p 12.1% (−0.9, 25.1; p Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; learning and school domain score (95%CI, p-value; effect size) −0.22 (−0.36, −0.08, p −0.16 (−0.31, −0.02, p Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; family domain score (95%CI, p-value; effect size) −0.21 (−0.36, −0.06, p −0.09 (−0.24, 0.06, p=0.242; 0.16)