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Efficacy and Safety of Lisdexamfetamine Dimesylate in Adolescents with Attention-Deficit/Hyperactivity Disorder

Saturday, 4 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
T. Banaschewski1, M. Gasior2, L. Squires2, R. Bloomfield3 and D. Coghill4, (1)Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty, Mannheim, University of Heidelberg, Mannheim, Germany, (2)Shire Development LLC, Wayne, PA, (3)Shire Pharmaceutical Development Ltd, Basingstoke, United Kingdom, (4)Division of Neuroscience, University of Dundee, Dundee, United Kingdom

The prodrug stimulant lisdexamfetamine dimesylate (LDX) is an effective, once-daily treatment for patients with attention-deficit/hyperactivity disorder (ADHD).


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.


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.


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.


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.

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