DR/ER-MPH Demonstrates Positive Phase 3 ADHD Results

An evening-dosed, delayed-release and extended-release, long-acting formulation of the stimulant methylphenidate (DR/ER-MPH) led to significant improvement in symptoms of children with attention-deficit/hyperactivity disorder (ADHD) compared to the placebo, according to the Journal of Child and Adolescent Psychopharmacology.

HLD200 consists of 2 layers of microbeads with an inner drug-loaded core. The drug formulation is designed to delay the initial release of drug by 8—10 hours, providing a controlled, extended drug release targeting the onset upon awakening, lasting into the evening.

“Developing new formulations of effective medications for patients with ADHD improves the lives of children with the disorder,” Harold S. Koplewicz, MD, editor-in-chief, Journal of Child and Adolescent Psychopharmacology, Child Mind Institute President, said.

While demonstrating ADHD symptom control, DR/ER-MPH is the first, long-acting MPH single dose formulation showing improvements in at-home early morning functioning impairment without compromising at-home functioning in the late afternoon and evening.

The evening dose represents a shift in the approach to timing of MPH delivery, providing a new treatment option specifically designed to address the unmet need for a once-daily ADHD medication providing efficacy upon awakening, but not at the expense of efficacy later throughout the day.

The 3-week, double-blind trial involved 161 6—12 years old with ADHD, randomized to receive HLD200 40–80 mg daily (n=81) or placebo (n=80).

Children taking HLD200 showed significant improvements in symptoms and at-home functional impairments in the early morning, late afternoon and evening after 3 weeks, versus children receiving the placebo.

The primary efficacy endpoint was the ADHD rating scale-IV, while 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 effects and 2 treatment-emergent adverse effects of special interest, appetite suppression and insomnia, with a direct questioning on sleep disturbance.

After 3 weeks, DR/ER-MPH was well tolerated, achieved significant improvements in ADHD symptoms versus the placebo, and at-home functional impairments in the early morning, late afternoon and evening in children with ADHD.

Main adverse effects, included insomnia and decreased appetite which were reported with other formulations of methylphenidate. All sleep related treatment-emergent adverse effects were mild or moderate in severity, with a majority reported as mild. One participant on the placebo experienced a sleep-related event leading to discontinuation of the study drug, while 4 participants on DR/ER-MPH experienced sleep-related events that resulted in a decrease in the dose. All appetite-related treatment-emergent adverse effects were mild or moderate in severity and all but 2 were resolved over the course of the study.

One participant receiving DR/ER-MPH reported mood swings, while 4 receiving the placebo had treatment-emergent adverse effects leading to early study withdrawal.

A recent survey revealed that of 201 primary caregivers of youth with ADHD, 75.6% of caregivers regarded the early morning as a time associated with moderate-to-severe ADHD-related functional impairment in the children, despite routine morning administration of stimulant medication.

Findings were corroborated by another survey of 350 primary caregivers of youth with and without ADHD that also found early morning functional impairment in stimulant-treated youth with ADHD significantly diminished the emotional well-being of caregivers, exerting a functional burden on the unit. The findings suggest inadequately controlled early morning ADHD symptoms and early morning functional impairment remain a significant burden on stimulant-treated youth with ADHD and their families.

The study, “Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder,” can be found in The Journal of Child and Adolescent Psychopharmacology.