Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension.

Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤17 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for ADHD and ha...

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Published in:Journal of Child & Adolescent Psychopharmacology Vol. 31; no. 9; pp. 610 - 623
Main Authors: Weiss, Margaret D., Cutler, Andrew J., Kollins, Scott H., Donnelly, Graeme A.E.
Format: research tables/charts randomized controlled trial Journal Article
Published: Mary Ann Liebert, Inc. Nov2021
Online Access:View this record in EBSCOhost
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      dt: Nov2021
      vid: 31
      iid: 9
      pid: 1365
      pub: Mary Ann Liebert, Inc.
      place: New Rochelle, New York
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        10.1089/cap.2021.0034
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        atl: Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension.
      aug:
        au:
          Weiss, Margaret D.
          Cutler, Andrew J.
          Kollins, Scott H.
          Donnelly, Graeme A.E.
        affil: Child and Adolescent Psychiatry, Cambridge Health Alliance, Cambridge, Massachusetts, USA.
      sug:
        subj:
          Attention Deficit Hyperactivity Disorder Drug Therapy
          Central Nervous System Stimulants Adverse Effects
          Methylphenidate Adverse Effects
          Human
          Adolescence
          Dose-Response Relationship, Drug
          Delayed-Action Preparations Therapeutic Use
          Treatment Outcomes
          Double-Blind Studies
          Comparative Studies
          Multicenter Studies
          Evaluation Research
          Validation Studies
          Clinical Assessment Tools
          Randomized Controlled Trials
          Adolescent: 13-18 years
      ab: Objectives: To study the safety and efficacy of the long-acting methylphenidate formulation PRC-063 in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Adolescents 12 to ≤17 years who met Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for ADHD and had a baseline ADHD Rating Scale DSM-5 (ADHD-5-RS) score ≥24 participated in a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study. Participants were randomized 1:1:1:1:1 to receive placebo or one of four doses of PRC-063 once daily for 4 weeks. The primary endpoint was change from baseline in least-squares mean clinician-rated ADHD-5-RS total score for PRC-063 (all doses combined) versus placebo. Other efficacy assessments included Conners third Edition: Self-Report (C3SR) and Clinical Global Impression-Improvement (CGI-I). A subset of double-blind study participants entered a subsequent open-label, dose-optimized study. Safety outcomes in both studies included treatment-emergent adverse events (TEAEs). Results: Three hundred fifty-four participants were included in the primary analysis. The least-squares mean change from baseline in ADHD-5-RS total score was -15.17 for PRC-063 versus -10.98 for placebo (least-squares mean difference -4.2, p = 0.0067). For individual PRC-063 doses, improvements in ADHD-5-RS total score versus placebo were significant for 45 mg (p = 0.0155) and 70 mg (p = 0.0401), but not for 25 or 85 mg. A significant improvement for PRC-063 versus placebo was recorded for C3SR Inattention (p = 0.0168), but not for the other C3SR subscales. About 52.7% of participants randomized to PRC-063 were responders based on CGI-I versus 32.4% of those randomized to placebo (p = 0.0004). Further improvements in ADHD symptoms based on ADHD-5-RS were observed from 1 month through 6 months of open-label treatment (p < 0.0001). There were two serious adverse events (both during the open-label study), one of which (aggressive behavior) was assessed as related to study drug. The only TEAEs that occurred in >10% of participants during double-blind treatment were decreased appetite (20.1%) and headache (15.0%). Most TEAEs were of mild or moderate severity. Conclusion: PRC-063 significantly improved ADHD symptomatology in adolescents. It was generally well tolerated, with an AE profile consistent with other long-acting stimulants. NCT02139111 and NCT02168127.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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