Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial

Abstract

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).

Fig. 1

CPRS-R total score by study visit (full analysis set). a Absolute values and b LS mean changes from baseline. The overall CPRS-R total score for each visit was calculated as the mean of the three assessments across the day. *P < 0.05, **P ≤ 0.01, ***P < 0.001 versus placebo (based on the difference in LS mean change [active treatment − placebo] from baseline to endpoint). Data are presented as mean or LS mean change ± standard error of the mean. Endpoint is the last on-treatment, post-baseline visit with a valid CPRS-R score. Patients enrolled after a protocol amendment had CPRS-R assessments at visits 0, 4 and 7/ET only. A decrease in CPRS-R total score indicates an improvement in ADHD-related symptoms and behaviors. ADHD attention-deficit/hyperactivity disorder, CPRS-R Conners’ Parent Rating Scale-Revised, ET early termination, FU follow-up, LDX lisdexamfetamine dimesylate, LS least-squares, OROS-MPH osmotic-release oral system methylphenidate

Fig. 2

CPRS-R total score at baseline and endpoint by time of day (full analysis set). a Absolute CPRS-R total scores at baseline and endpoint and b LS mean changes from baseline to endpoint in CPRS-R total score by time of day. ***P < 0.001 versus placebo, based on the difference in LS mean change (active treatment − placebo) from baseline to endpoint. Data are presented as mean or LS mean change ± standard error of the mean. Dosing occurred at approximately 0700 hours. Endpoint is the last on-treatment, post-baseline visit with a valid CPRS-R score. Patients enrolled after a protocol amendment had CPRS-R assessments at visits 0, 4 and 7/ET only. A decrease in CPRS-R total score indicates an improvement in ADHD-related symptoms and behaviors. ADHD attention-deficit/hyperactivity disorder, CPRS-R Conners’ Parent Rating Scale-Revised, ET early termination, FU follow-up, LDX lisdexamfetamine dimesylate, OROS-MPH osmotic-release oral system methylphenidate