GW320659 for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children

To assess the safety, tolerability, and efficacy of GW320659, a chemically novel inhibitor of norepinephrine and dopamine reuptake, in pediatric attention-deficit/hyperactivity disorder (ADHD). This was a multicenter, open-label, dose-titration study of seven daily dose levels of GW320659: 1.25, 2.5, 5, 7.5, 10, 12.5, and 15 mg. Treatment began with the lowest dose of GW320659 and increased weekly until subjects (mean age 9.1 years) achieved a maximum acceptable dose. Subjects remained at their maximum acceptable dose for a 4-week treatment period. The key efficacy end-point was clinical response (Clinical Global Impressions of Improvement score of 1 or 2 and an improvement of 5 or more points on at least one of the Conners Parent or Teacher Rating Scales T score). Other end-points included assessments of safety and of quality of life using the Child Health Questionnaire Parent Form 28 (CHQ-PF28). Fifty-one subjects entered the titration phase and 46 subjects completed the study. During the treatment phase, these 46 subjects received a mean dose of 14.2 mg/day and the maximum exposure to GW320659 was 11 weeks. At the end of the treatment period, 76% of subjects showed improvement with GW320659 and there were significant improvements in 7 of the 12 subscales of the CHQ-PF28 compared with baseline (p < .05). Adverse events were generally mild; only five subjects required downward titration because of adverse events (three psychiatric, one neurological and urological, one cardiovascular), and no subject withdrew because of adverse events. GW320659 may have clinically relevant efficacy in pediatric ADHD and was well tolerated in this short-term initial study in children.