Efficacy and Safety of Multilayer, Extended-Release Methylphenidate (PRC-063) in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder: A Laboratory Classroom Study

J Child Adolesc Psychopharmacol. 2020 Dec;30(10):580-589. doi: 10.1089/cap.2020.0109. Epub 2020 Oct 22.

Abstract

Objective: To determine the safety and efficacy of PRC-063, a once-daily, multilayer, extended-release (ER) formulation of methylphenidate (MPH) hydrochloride, in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a randomized, double-blind, parallel group, dose-optimized, placebo-controlled phase 3 study. Methods: Boys and girls aged 6-12 years diagnosed with ADHD were enrolled. During a 6-week, open-label, dose-optimization phase, subjects began treatment at 25 mg/day of PRC-063 and were titrated until an optimal dose (maximum 85 mg/day) was reached. During the double-blind period, subjects were randomized to receive treatment with their optimal dose of PRC-063 or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of the double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). Safety was assessed measuring adverse events (AEs), vital signs, and electrocardiograms. Results: The study was completed by 147 subjects. In the primary efficacy analysis, significant improvements were demonstrated with PRC-063 versus placebo (p < 0.0001) when SKAMP-Combined scores were averaged over the 13-hour full-day laboratory classroom (least squares mean difference = -8.6, 95% confidence interval = -10.6 to -6.6). Mean average PERMP-Total scores were also significantly improved with PRC-063 versus placebo at all time points postdose (p < 0.01). The onset of treatment effect was present by 1-hour postdose (the first time point measured) and duration of efficacy was up to and including 13 hours postdose. AEs reported in ≥5% of subjects during the dosing optimization period were decreased appetite, abdominal pain upper, affect lability, weight decreased, headache, irritability, and insomnia. Conclusions: PRC-063 was effective in improving attention and reducing symptoms of ADHD versus placebo and had a rapid onset and extended duration of effect. AEs were consistent to those reported with other ER MPH treatments. Clinical Trial Registry: NCT03172481.

Keywords: Adhansia; Foquest; PRC-063; attention-deficit/hyperactivity disorder; laboratory classroom study; methylphenidate.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methylphenidate / adverse effects
  • Methylphenidate / therapeutic use*
  • Treatment Outcome

Substances

  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Methylphenidate

Associated data

  • ClinicalTrials.gov/NCT03172481