Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder.

Content Provider	Europe PMC
Author	Pliszka, Steven R. Wilens, Timothy E. Bostrom, Samantha Arnold, Valerie K. Marraffino, Andrea Cutler, Andrew J. López, Frank A. DeSousa, Norberto J. Sallee, Floyd R. Incledon, Bev Newcorn, Jeffrey H.
Copyright Year	2017
Abstract	Abstract Objective: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) formulation consisting of uniform, dual-layered microbeads with an inner drug-loaded core. DR/ER-MPH is designed to delay the initial release of drug by 8–10 hours, and thereafter, provide a controlled, extended drug release to target onset of effect upon awakening that lasts into the evening. This phase 3 study evaluated the safety and efficacy of DR/ER-MPH on symptoms and temporal at-home functional impairment in children with attention-deficit/hyperactivity disorder (ADHD). Methods: This 3-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, forced-dose titration trial evaluated DR/ER-MPH (40–80 mg/day) in children aged 6–12 years with ADHD. Primary efficacy endpoint was the ADHD rating scale–IV (ADHD-RS-IV), and the key secondary endpoints were the Before-School Functioning Questionnaire (BSFQ), and Parent Rating of Evening and Morning Behavior-Revised, morning (PREMB-R AM) and evening (PREMB-R PM). Safety measures included spontaneously reported treatment-emergent adverse events (TEAEs) and two TEAEs of special interest, appetite suppression and insomnia (with direct questioning on sleep disturbance). Results: One hundred sixty-one participants were included in the intent-to-treat population (DR/ER-MPH, n = 81; placebo, n = 80). After 3 weeks, DR/ER-MPH achieved significant improvements versus placebo in ADHD symptoms (least-squares [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; p = 0.002), and at-home early morning (LS mean BSFQ: 18.7 vs. 28.4; p < 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; p < 0.001) and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; p = 0.002) functional impairment. Commonly reported TEAEs (≥10%) were insomnia and decreased appetite. Conclusions: DR/ER-MPH was generally well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and at-home functional impairments in the early morning, late afternoon, and evening in children with ADHD.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5567875&blobtype=pdf
Page Count	9
ISSN	10445463
Volume Number	27
DOI	10.1089/cap.2017.0084
PubMed Central reference number	PMC5567875
Issue Number	6
PubMed reference number	29172680
Journal	Journal of Child and Adolescent Psychopharmacology [J Child Adolesc Psychopharmacol]
e-ISSN	15578992
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2017-07-21
Publisher Place	USA
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © Steven R. Pliszka et al. 2017; Published by Mary Ann Liebert, Inc.
Subject Keyword	methylphenidate delayed-release extended-release attention-deficit/hyperactivity disorder functioning symptoms
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Psychiatry and Mental Health Pediatrics, Perinatology and Child Health