Efficacy and Safety of HLD200, Delayed-Release and Extended-Release Methylphenidate, in Children with Attention-Deficit/Hyperactivity Disorder
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OBJECTIVE: Evening-dosed HLD200 is a delayed-release and extended-release methylphenidate (DR/ER-MPH) formulation consisting of uniform, dual-layered microbeads with an inner drug-loaded core. DR/ER-MPH is designed to delay the initial release of drug by 8-10 hours, and thereafter, provide a controlled, extended drug release to target onset of effect upon awakening that lasts into the evening. This phase 3 study evaluated the safety and efficacy of DR/ER-MPH on symptoms and temporal at-home functional impairment in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This 3-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group, forced-dose titration trial evaluated DR/ER-MPH (40-80 mg/day) in children aged 6-12 years with ADHD. Primary efficacy endpoint was the ADHD rating scale-IV (ADHD-RS-IV), and the 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). Safety measures included spontaneously reported treatment-emergent adverse events (TEAEs) and two TEAEs of special interest, appetite suppression and insomnia (with direct questioning on sleep disturbance). RESULTS: One hundred sixty-one participants were included in the intent-to-treat population (DR/ER-MPH, n = 81; placebo, n = 80). After 3 weeks, DR/ER-MPH achieved significant improvements versus placebo in ADHD symptoms (least-squares [LS] mean ADHD-RS-IV: 24.1 vs. 31.2; p = 0.002), and at-home early morning (LS mean BSFQ: 18.7 vs. 28.4; p < 0.001; LS mean PREMB-R AM: 2.1 vs. 3.6; p < 0.001) and late afternoon/evening (LS mean PREMB-R PM: 9.4 vs. 12.2; p = 0.002) functional impairment. Commonly reported TEAEs (≥10%) were insomnia and decreased appetite. CONCLUSIONS: DR/ER-MPH was generally well tolerated and demonstrated significant improvements versus placebo in ADHD symptoms and at-home functional impairments in the early morning, late afternoon, and evening in children with ADHD.
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The types of TEAEs reported with DR/ER-MPH were similar to those seen with other methylphenidates.
“and the types of TEAEs reported were similar to those seen with other methylphenidates (A. C. Childress et al., 2020; Pliszka et al., 2017).”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Pliszka et al., 2017
As DR/ER-MPH is evening-dosed, there is no lag time between awakening and onset of effect, which reduces overall ADHD functional impairment in the early morning.
“As DR/ER-MPH is evening-dosed, there is no lag time between awakening and onset of effect, which reduces overall ADHD functional impairment in the early morning (A. C. Childress et al., 2020; Pliszka et al., 2017).”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Pliszka et al., 2017
Studies with DR/ER-MPH have shown significant improvements in ADHD functional impairment in both the morning and evening using validated rating scales such as the Parent Rating of Evening and Morning Behavior Scale-Revised.
“Studies with DR/ER-MPH have shown significant improvements in ADHD functional impairment in both the morning and evening using validated rating scales such as the Parent Rating of Evening and Morning Behavior Scale—Revised (A. C. Childress et al., 2020; Pliszka et al., 2017).”
From A Post-Hoc Analysis of Emotional Lability With Delayed-Release/Extended-Release Methylphenidate in Children Aged 6 to 12 Years of Age Participating in Two Phase 3 Clinical Trials (2024) · cites this paper as Pliszka et al., 2017
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Arnold, V. K., López, F. A., Childress, A. C., Po, M. D., Uchida, C. L., Cuthbertson, L., Sallee, F. R., & Incledon, B. (2024) · Journal of Attention Disorders · doi:10.1177/10870547241243155 · Cited by 1 · see citing works
“Childress et al., 2020; Pliszka et al., 2017).”
BackgroundMethodResultInfluentialSelf-citation
- Authors
- Pliszka, S. R., Wilens, T. E., Bostrom, S., Arnold, V. K., Marraffino, A., Cutler, A. J., López, F. A., DeSousa, N. J., Sallee, F. R., Incledon, B., Newcorn, J. H., & On behalf of the HLD200-108 Study Group
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Massachusetts General Hospital (US)
- Westside Medical Family Practice, Clinton, Utah.
- University of Tennessee Health Science Center (US)
- Meridien Research (US)
- Children's Developmental Center, Winter Park, Florida.
- Ironshore Pharmaceuticals & Development, Inc., Grand Cayman, Cayman Islands.
- Mount Sinai Medical Center, New York, New York.
- Corresponding author
- Pliszka, Steven R.
- ORCID
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-08
- Volume
- 27
- Issue
- 6
- Pages
- 474-482
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC5567875
- OpenAlex
- W2738856406
- Cited by
- 44
- References
- 7
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 1
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Massachusetts General Hospital
- Teva Pharmaceutical Industries
- Purdue University
- Major League Baseball
- Sunovion
- Neos Therapeutics
- Arbor Pharmaceuticals
- Cerecor
- Shionogi
- H. Lundbeck A/S
- National Institutes of Health
- Allergan
- National Institute on Drug Abuse
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Keywords
- extended-release methylphenidate, attention deficit hyperactivity disorder, children, evening dosing, sustained drug release, functional disability, ADHD-RS-IV, insomnia, appetite suppression, treatment-emergent adverse events, parent-reported behavior
- MeSH terms
- Central Nervous System Stimulants, Appetite, Attention Deficit Disorder with Hyperactivity, Child, Delayed-Action Preparations, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Humans, Sleep Initiation and Maintenance Disorders, Male, Methylphenidate, Treatment Outcome
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