A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder

Abstract

Background: Lisdexamfetamine dimesylate (LDX) is indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years of age and in adults. In a previous laboratory school study, LDX demonstrated efficacy 2 hours postdose with duration of efficacy through 12 hours. The current study further characterizes the time course of effect of LDX.

Methods: Children aged 6 to 12 years with ADHD were enrolled in a laboratory school study. The multicenter study consisted of open-label, dose-optimization of LDX (30, 50, 70 mg/d, 4 weeks) followed by a randomized, placebo-controlled, 2-way crossover phase (1 week each). Efficacy measures included the SKAMP (deportment [primary] and attention [secondary]) and PERMP (attempted/correct) scales (secondary) measured at predose and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 hours postdose. Safety measures included treatment-emergent adverse events (AEs), physical examination, vital signs, and ECGs.

Results: A total of 117 subjects were randomized and 111 completed the study. Compared with placebo, LDX demonstrated significantly greater efficacy at each postdose time point (1.5 hours to 13.0 hours), as measured by SKAMP deportment and attention scales and PERMP (P < .005). The most common treatment-emergent AEs during dose optimization were decreased appetite (47%), insomnia (27%), headache (17%), irritability (16%), upper abdominal pain (16%), and affect lability (10%), which were less frequent in the crossover phase (6%, 4%, 5%, 1%, 2%, and 0% respectively).

Conclusion: In school-aged children (6 to 12 years) with ADHD, efficacy of LDX was maintained from the first time point (1.5 hours) up to the last time point assessed (13.0 hours). LDX was generally well tolerated, resulting in typical stimulant AEs.

Trial registration: Official Title: A Phase IIIb, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Dose-Optimization, Cross-Over, Analog Classroom Study to Assess the Time of Onset of Vyvanse (Lisdexamfetamine Dimesylate) in Pediatric Subjects Aged 6-12 With Attention-Deficit/Hyperactivity Disorder. ClinicalTrials.gov Identifier: NCT00500149 http://clinicaltrials.gov/ct2/show/NCT00500149.

Figure 1

Study design. V: visit; LDX: lisdexamfetamine dimesylate.

Figure 2

Time course of SKAMP-D (closed symbols) and SKAMP-A (open symbols) assessment over the laboratory school day. LS mean (SE) actual scores (top) and change from predose (bottom) for LDX (squares) and placebo (circles) at predose (-0.5 h) and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 h postdose. Scores were compared using a linear mixed model with sequence, period, and treatment as fixed effects and subject within sequence as a random effect. Lower scores denote improvement. *Denotes P < .005 LDX compared with placebo for SKAMP-D. ^†Denotes P ≤ .001 LDX compared with placebo for SKAMP-A.

Figure 3

Time course of PERMP-A (closed symbols) and PERMP-C (open symbols) assessment over the laboratory school day. LS mean (SE) actual scores (top) and change from predose (bottom) for LDX (squares) and placebo (circles) at predose (-0.5 h) and at 1.5, 2.5, 5, 7.5, 10, 12, and 13 h postdose. Scores were compared using a linear mixed model with sequence, period, and treatment as fixed effects and subject within sequence as a random effect. Higher scores denote improvement. *Denotes P < .0001 LDX compared with placebo for PERMP-A. ^†Denotes P < .0001 LDX compared with placebo for PERMP-C.