Building: Bourbon Cataratas Convention Centre, Foz do Iguaçu
Room: Iguazu I
Date: 2014-05-06 03:30 PM – 03:45 PM
Last modified: 2014-02-09
Abstract
Introduction
Data will be presented on the systemic exposure to d-amfetamine and the duration of therapeutic action of the d-amfetamine prodrug lisdexamfetamine dimesylate (LDX).
Methods
In study NRP104.103, plasma d‑amfetamine was measured after single doses of LDX (30mg, 50mg or 70mg) in patients (6–12 years) with attention-deficit/hyperactivity disorder (ADHD). Study SPD489-325 was a 7-week, randomized, double-blind, placebo- and active-controlled trial of LDX (30mg, 50mg or 70mg) in patients (6–17 years) with ADHD. Osmotic-release oral system methylphenidate (OROS-MPH) was the reference treatment. On days 0, 28 and 49, patients were assessed using the Conners’ Parent Rating Scale-Revised (CPRS-R) at 10:00, 14:00 and 18:00hrs following dosing at 07:00hrs.
Results
Of 18 patients randomized in NRP104.103, 17 completed the study. Plasma d‑amfetamine concentrations peaked with mean Tmax in the range 3.41–3.58h, and declined with mean half-life in the range 8.61–8.90h. Of 336 patients randomized in SPD489-325, 317 comprised the full analysis set and 196 completed the study. Compared with placebo, both LDX and OROS-MPH treatment significantly improved CPRS‑R scores at all three assessment times (p<0.001) with effect sizes of 1.424, 1.411 and 1.300 for LDX and 1.036, 0.976 and 0.922 for OROS-MPH, respectively. Post-hoc analyses showed improvements were significantly greater (p<0.02) for LDX than OROS-MPH, with effect sizes of 0.387, 0.435 and 0.377 at each time point.
Conclusion
Following an early morning dose of LDX, improvements in CPRS-R scores in children with ADHD are maintained throughout the day, consistent with the plasma d‑amfetamine concentration-time profile.
Supported by funding from Shire.