Background: In a pivotal, randomized, double-blind, placebo-controlled, phase 3 trial of children (6–12y) with ADHD (NCT02520388), treatment with HLD200, an evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) significantly improved ADHD symptoms and reduced early morning and late afternoon/evening at-home functional impairment. This post hoc analysis evaluated the clinical meaningfulness of functional impairment improvements with DR/ER-MPH versus placebo.
Methods: At-home early morning functional impairment was assessed by the 20-item Before School Functioning Questionnaire (BSFQ) and 3-item Parent Rating of Evening and Morning Behavior-Revised (PREMB-R) AM subscale. At-home late afternoon/evening functional impairment was assessed by the 8-item PREMB-R PM subscale. Items on all measures were rated 0 (none) to 3 (severe). Clinically meaningful improvements in functional impairment were defined using Clinical Global Impression-Improvement (CGI-I) scores of 1 (very much improved) and ≤2 (very much/much improved). Cumulative percentages of children with changes from baseline in BSFQ, PREMB-R AM, and PREMB-R PM anchored to CGI-I were evaluated; chi-square tests assessed treatment differences.
Results: Reductions from baseline of 20, 3, and 5 on BSFQ, PREMB-R AM, and PREMB-R PM, respectively, were defined as clinically meaningful when anchored to CGI-I≤2. Significantly more children receiving three weeks of DR/ER-MPH treatment versus placebo achieved these clinically meaningful improvements in BSFQ (65.4% vs 43.3%; P<0.05), PREMB-R AM (73.4% vs 41.3%; P<0.001), and PREMB-R PM (64.6% vs 42.7%; P<0.05). Differences were also significant when anchoring to CGI-I=1. TEAEs were consistent with MPH.
Conclusions: This post hoc analysis suggests that improvements in at-home functional impairment with DR/ER-MPH treatment are clinically meaningful.