Efficacy and Safety of a Delayed-Release and Extended-Release Methylphenidate Formulation in Children With ADHD: Results From a Pivotal Phase 3 Trial in a Naturalistic Setting

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. This pivotal, phase 3, forced-dose titration trial sought to determine whether DR/ER-MPH improves control of attention-deficit/hyperactivity disorder (ADHD) symptoms and early morning and late afternoon/evening functional impairment versus placebo in 161 children (6–12 years) with ADHD (NCT02520388).

Methods: Following a screening/washout period of ≤2 weeks, participants were randomized (1:1) to double-blind DR/ER-MPH or placebo administered in the evening for 3 weeks. The initial 40-mg dose was titrated weekly in 20-mg increments to 60 mg and 80 mg, as tolerated, with one down-titration step permitted. The primary endpoint was the ADHD Rating Scale-IV (ADHD-RS-IV) Total Score. 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) subscales. Safety measures included treatment-emergent adverse events (TEAEs).

Results: Mean DR/ER-MPH dose after 3 weeks was 68.1 mg. After 3 weeks, children on DR/ER-MPH (n=81) achieved significant improvements versus those on placebo (n=80) in ADHD symptoms (ADHD-RS-IV; P=0.002), early morning functional impairment (BSFQ; P < 0.001; PREMB-R AM; P < 0.001), and late afternoon/evening functional impairment (PREMB-R PM; P=0.002). The most common TEAEs (≥10%) reported by children on DR/ER-MPH were decreased appetite and any insomnia.

Conclusion: Following daily evening administration, DR/ER-MPH was well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and early morning and late afternoon/evening functional impairment in children with ADHD.

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