130 Consistent Efficacy of DR/ER-MPH on Early Morning Functioning in Children With ADHD: Analysis of BSFQ Item Ratings From a Pivotal Phase 3 Trial

Abstract

Objective

In a phase 3 trial of children with attention-deficit/hyperactivity disorder (ADHD), DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairment versus placebo. The validated Before School Functioning Questionnaire (BSFQ), a key secondary endpoint, was used to measure early morning functional (EMF) impairment. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo on individual BSFQ item scores from baseline.

Method

Data were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 20-item BSFQ, investigators evaluated EMF impairment by scoring each item on a severity scale of 0 to 3, with 0 denoting “no impairment” and 3 denoting “severe impairment”. For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual BSFQ items score derived from an analysis of covariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.

Results

Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean BSFQ item scores frombaseline on 18 out of 20 items versus placebo (P<0.001 in 8 items [listening, following directions, attention, forgetfulness, talkativeness, silliness, time awareness, getting to school]; P<0.01 in 7 items [overall organization, being quiet, distraction, interrupt/blurt out, breakfast, hygiene, independence]; P<0.05 in 3 items [procrastination, hyperactivity, awaiting turn]). Only “dressing” and “misplacing/losing items” showed no significant between-group differences (P=0.171 and P=0.175, respectively). Distributions of the severity ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent with methylphenidate.

Conclusions

Post hoc analyses revealed that DR/ER-MPH significantly reduced 18 out of 20 individual BSFQ item scores versus placebo in children with ADHD. These findings are worth further exploration.

Funding Acknowledgements

Ironshore Pharmaceuticals & Development, Inc.