A Randomized, Double-Blind, Placebo-Controlled Study of Delayed-Release and Extended-Release Methylphenidate in Children With ADHD: An Evaluation of Safety and Efficacy Throughout the Day and Across Settings

Purpose: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) designed to provide treatment effect in the early morning, throughout the day, and into the evening. Herein, we present the efficacy and safety of DR/ER-MPH from a pivotal phase 3 study of 125 children (6–12 years) with attention-deficit/hyperactivity disorder (ADHD) (NCT02493777).

Methods: During a 6-week open-label phase, dose and administration time of DR/ER-MPH were optimized based on ADHD Rating Scale-IV, Before School Functioning Questionnaire, and Conners’ Global Index – Parent. Participants were then randomized 1:1 to double-blind optimized DR/ER-MPH or placebo for 1 week. Functional impairment was assessed using the model-adjusted average of post-dose Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale combined scores (SKAMP CS) from 8:00 AM to 8:00 PM and Parent Rating of Evening and Morning Behavior-Revised, Morning (PREMB-R AM) and Evening (PREMB-R PM) subscales. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results: After the open-label phase, DR/ER-MPH was most commonly administered at 8:00 PM and mean dose was 66.2 mg/d. During the double-blind phase (DR/ER-MPH, n=64; placebo, n=53), DR/ER-MPH treatment significantly improved functional impairment versus placebo in the early morning (PREMB-R AM; P < 0.001), throughout the classroom day (model-adjusted SKAMP CS; P < 0.001), and in the late afternoon/evening (PREMB-R PM; P=0.003). Most TEAEs were mild/moderate and no serious TEAEs were reported; incidence of TEAEs was similar between double-blind treatment groups.

Conclusion: DR/ER-MPH was well tolerated and improved ADHD-related symptoms and functional impairment in the early morning and throughout the day versus placebo in children with ADHD.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.