Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study.

Background: Extended-release guanfacine hydrochloride (GXR), a selective alpha 2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD. Methods: Children/adolescents (6-17 years) with ADHD received open-label GXR (1-7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (>= 50% increase in ADHD Rating Scale version IV total score and >= 2-point increase in Clinical Global Impression-Severity compared with RWP baseline, at two consecutive visits). The key secondary endpoint was time to treatment failure (TTF). Trial registration: ClinicalTrials.gov identifier NCT01081145; EudraCT 2009-018161-12. Results: A total of 528 participants enrolled; 316 (59.8%) entered the RWP. Treatment failure occurred in 49.3% of the GXR and 64.9% of the placebo group (p = 0.006). TTF was significantly longer in GXR versus placebo (p = 0.003). GXR was well tolerated. Conclusions: Guanfacine hydrochloride demonstrated long-term maintenance of efficacy compared with placebo in children/adolescents with ADHD. Implications of the placebo substitution design and findings with different ADHD medications are discussed.