A Randomized Placebo-Controlled Double-Blind Study Evaluating the Time Course of Response to Methylphenidate Hydrochloride Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extendedrelease multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting. Methods: This randomized double-blind placebo-controlled study included children 6-12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period ( £ 4 weeks) and a 2 day medication washout period; 2) openlabel period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2-4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0-12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance. Results: The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p = 0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0-12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo ( p £ 0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study. Conclusions: MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6-12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose.

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder

“…Two randomized, double-blind (DB), placebo-controlled, phase 3 studies were included in the MPH-MLR clinical development program (Wigal et al 2014, 2015). Study 1 ( Identifier: NCT01269463) evaluated the time course of response to MPH-MLR in an analog classroom setting (Wigal and Wigal 2006) and included four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), DB crossover (2 weeks), and follow-up call (Wigal et al 2014).…”

“…Study 1 ( Identifier: NCT01269463) evaluated the time course of response to MPH-MLR in an analog classroom setting (Wigal and Wigal 2006) and included four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), DB crossover (2 weeks), and follow-up call (Wigal et al 2014). Children (male or female) aged 6–12 years at the time of consent with any of the three subtypes of ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders , fourth edition, text revision (DSM-IV-TR) (American Psychiatric Association 2000) were eligible for inclusion in the study.…”

“…In an analog classroom study (Study 1), significant improvements in ADHD symptoms were observed 1 hour after administration of MPH-MLR and sustained for ≥12 hours, with no diminution of effect (Wigal et al 2014). The pivotal studies supporting marketing approval for MPH-MLR demonstrated that it is efficacious for ADHD in children and adolescents, as evaluated in both analog classroom and outpatient environments (Wigal et al 2014, 2015).…”

“…The pivotal studies supporting marketing approval for MPH-MLR demonstrated that it is efficacious for ADHD in children and adolescents, as evaluated in both analog classroom and outpatient environments (Wigal et al 2014, 2015). …”

New Insights into the Pathogenesis and Pharmacogenomics of Attention Deficit Hyperactivity Disorder

“…Efficacious and well-tolerated medications are available for the treatment of ADHD (methylphenidate, ethylphenidate, lisdexamfetamine, atomoxetine, metadoxine, guanfacine) [31][32][33][34][35][36][37][38][39]. Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration (FDA) for the treatment of ADHD in children.…”