Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

Timothy Wigal, Matthew Brams, Maria Gasior, Joseph Gao, Liza Squires, John Giblin, 316 Study Group, Timothy Wigal, Matthew Brams, Maria Gasior, Joseph Gao, Liza Squires, John Giblin, 316 Study Group

Abstract

Background: Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace environment.

Methods: After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.

Results: Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P <or= .0017 for each time point) and change from predose (P < .001 for each time point) PERMP total scores were greater at all postdose time points from 2 to 14 h for adults while receiving LDX vs placebo. LDX demonstrated efficacy vs placebo (P < .0001) by the difference in LS mean (95% CI) for ADHD-RS-IV total scores: -11.5 (-14.2, -8.9). TEAEs (>or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX.

Conclusions: LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD.

Trial registration: ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1.

Figures

Figure 1
Figure 1
Study design. (AWE = adult workplace environment; LDX = lisdexamfetamine dimesylate).
Figure 2
Figure 2
LS Mean (SE) change from predose in PERMP total score from 2 to 14 hours postdose (n = 104/104). (LDX = lisdexamfetamine dimesylate; LS = least squares; PERMP = Permanent Product Measure of Performance). LDX-purple diamonds; Placebo-green circles. * P < .001 LDX vs placebo.
Figure 3
Figure 3
LS mean (SE) change from predose in PERMP-A and PERMP-C scores from 2 to 14 hours postdose (n = 104/104). (LDX = lisdexamfetamine dimesylate; LS = least squares; PERMP-A/-C = Permanent Product Measure of Performance-Attempted/-Correct). PERMP-A: LDX-purple diamonds; Placebo-green diamonds; PERMP-C: LDX-blue circles; Placebo-orange circles.* P < .001 LDX vs placebo.
Figure 4
Figure 4
ADHD-RS-IV total scores at baseline and visit 5/6 and difference in LS mean (95% CI) between LDX and placebo during the double-blind crossover phase. (ADHD-RS-IV = Attention-Deficit/Hyperactivity Disorder Rating Scale IV; CI = confidence interval; LDX = lisdexamfetamine dimesylate; LS = least squares). * P < .0001 LDX vs placebo.

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