le-blind randomized withdrawal phase.
Paediatric population
The effects of lisdexamfetamine dimesylate in the treatment of paediatric patients with ADHD have been demonstrated in three controlled trials in children aged 6 to 12 years, three controlled studies in adolescents aged 13 to 17 years, and three controlled studies in children and adolescents aged 6 to 17 years.
In study SPD489-325, 336 patients aged 6 to17 years were eva luated in a 7-week randomised double-blind, dose-optimised, placebo controlled with an active reference arm study. The primary efficacy assessment was the ADHD-RS-IV Total Score. Lisdexamfetamine dimesylate showed significantly greater efficacy than placebo. The difference at Endpoint in least square means reduction from baseline in the ADHD-RS-IV Total Score was 18.6 (p<0.001). At every on-treatment visit and at Endpoint the percentages of subjects who met pre-defined response criteria (a ≥30% reduction from Baseline in ADHD-RS-IV Total Score and a CGI-I value of 1 or 2) was significantly higher for lisdexamfetamine dimesylate when compared to placebo (p<0.001). In addition, mean scores for ADHD symptoms following treatment discontinuation did not exceed baseline scores prior to treatment, indicating there was no rebound effect. In addition to a reduction in symptoms, lisdexamfetamine dimesylate significantly improved functional outcomes. In this study, 75.0% of subjects receiving lisdexamfetamine dimesylate showed “improvement” (defined as “very much improved” or “much improved”) on the CGI-I rating scale compared to 14.2% on placebo (p<0.001).
Similar results for ADHD-RS Total Score and CGI-I have been shown in two placebo controlled studies, one in children (n=297) and the other in adolescents (n=314), both conducted in the United States.
A double-blind, randomised, active-controlled, dose-optimisation study was conducted in children and adolescents aged 6 to 17 years (n=267) who met DSM-IV criteria for ADHD and also had an inadequate response to methylphenidate treatment. In this 9-week study, patients treated with lisdexamfetamine dimesylate had a shorter time to first response compared to patients treated with atomoxetine (median 13.0 vs 21.0 days, respectively; p=0.003), where response was defined as having a CGI-I score of 1 (very much improved) or 2 (much improved) at any of the double-blind treatment visits.
Two double-blind, parallel-group, active-controlled (OROS-MPH) studies have been conducted in adolescents aged 13-17 years with ADHD. Both studies also included a placebo reference arm. The 8-week dose-optimization study (SPD489-405) had a 5-week dose- optimization period and a 3-week dose-maintenance period. During the dose-optimization period, subjects were titrated once weekly based on TEAEs and clinical response to an optimal dose of 30, 50, or 70 mg/day (for SPD489 subjects) or 18, 36, 54, or 72 mg/day (for OROS-MPH subjects), which was maintained throughout a 3-week dose-maintenance period. The mean doses at endpoint were 57.9 mg and 55.8 mg for SPD489 and OROS-MPH, respectively. In this study, neither SPD489 nor OROS-MPH was found to be statistically superior to the other product at Week 8. The 6-week fixed-dose study (SPD489-406) had a 4- week forced-dose titration period and a 2-week dose-maintenance period. At the highest doses of SPD489 (70 mg) and OROS-MPH (72 mg), SPD489 treatment was found to be superior to OROS-MPH as measured by bot |
