Jeffrey H Newcorn1, Valerie Harpin2, Michael Huss3, Andrew Lyne4, Vanja Sikirica5, Mats Johnson6, Josep Antoni Ramos-Quiroga7,8, Judy van Stralen9, Benoit Dutray10, Sasha Sreckovic11, Ralph Bloomfield4, Brigitte Robertson5. 1. Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Ryegate Children's Centre, Sheffield NHS Foundation Trust, Sheffield, UK. 3. Johannes Gutenberg-University Mainz, Mainz, Germany. 4. Shire, Basingstoke, UK. 5. Shire, Wayne, PA, USA. 6. Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden. 7. Department of Psychiatry, CIBERSAM, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 8. Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. 9. Center for Pediatric Excellence, Ottawa, ON, Canada. 10. Centre Hospitalier de Rouffach, Rouffach, France. 11. Shire, Eysins, Switzerland.
Abstract
BACKGROUND: Extended-release guanfacine hydrochloride (GXR), a selective α2A-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 receivedopen-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.
RCT Entities:
BACKGROUND: Extended-release guanfacine hydrochloride (GXR), a selective α2A-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.
Authors: Shweta Anand; Henry Tong; Frank M C Besag; Esther W Chan; Samuele Cortese; Ian C K Wong Journal: Paediatr Drugs Date: 2017-06 Impact factor: 3.022
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