The prodrug stimulant lisdexamfetamine dimesylate (LDX) is an effective, once-daily treatment for patients with attention-deficit/hyperactivity disorder (ADHD).
Objectives:
To evaluate the efficacy and safety of LDX in adolescent patients with ADHD in a European, randomized, double-blind, phase 3 trial. Results are compared with those of an earlier US-based study of LDX in adolescent patients with ADHD.
Methods:
SPD489-325 was a European, 7-week, randomized, placebo-controlled trial of an optimized daily dose of LDX (30mg, 50mg or 70mg) in children (aged 6–12 years) and adolescents (aged 13–17 years) with ADHD; osmotic-release oral system methylphenidate (OROS-MPH, 18mg, 36mg or 54mg) was included as a reference arm. SPD489-305 was a US-based, 4-week, forced-dose titration, double-blind study, in which adolescents (aged 13–17 years) with ADHD were randomized equally to once-daily LDX 30mg, 50mg or 70 mg or placebo. For both studies, the primary efficacy measure was the change from baseline in ADHD Rating Scale version IV (ADHD-RS-IV) total score at endpoint (last on-therapy, post-randomization visit). Safety assessments included, but were not limited to, treatment-emergent adverse events (TEAEs) and vital signs.
Results:
In study SPD489-325, a total of 336 patients were randomized and 88 adolescents (aged 13–17 years) were included in the full analysis set (FAS). At endpoint, placebo-adjusted least-squares (LS) mean changes from baseline (95% confidence interval [CI]) in ADHD-RS-IV total scores in adolescents were: LDX, –20.8 (–25.7, –16.0); OROS-MPH, –8.1 (–13.0, –3.3) (p<=0.001 for both comparisons versus placebo). Consistent with the known effects of stimulant treatment, TEAEs reported by >=10% of adolescents receiving LDX included decreased appetite, headache, decreased weight and insomnia. In SPD489-305, 314 adolescents were randomized and 309 were included in the FAS. At endpoint, the differences (LDX – placebo) in LS mean changes from baseline (95% CI) in ADHD-RS-IV total scores for LDX were: 30mg, –5.5 (–9.7, –1.3); 50mg, –8.3 (–12.5, –4.1); 70mg, –7.9 (–12.1, –3.8) (p<0.01 for each comparison versus placebo). TEAEs reported by >=10% of adolescents receiving LDX were decreased appetite, headache and insomnia.
Conclusions:
LDX was effective and generally well tolerated in a subgroup of patients aged 13–17 years with ADHD in this European phase 3 trial. Results were generally consistent with those of an earlier, US-based clinical trial of LDX in adolescents with ADHD.