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

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.

Conflict of interest statement

A.C.C. has received research support from Akili, Allergan, Alcobra, Arbor, Emalex, Forest, Ironshore, KemPharm, Lilly, Lundbeck, Medgenics, Neos, Neurovance, NextWave, NLS, Noven, Otsuka, Pearson, Pfizer, Purdue Pharma (Canada), Rhodes Pharmaceuticals L.P., Servier, Shire, Sunovion, Supernus, Theravance, and Tris; been a consultant for and received honoraria from Kempharm, Ironshore, Neos, Pfizer, Rhodes Pharmaceuticals L.P., Shire, Sunovion, Supernus and Tris; received travel support from Adlon, Ironshore, NextWave, Pfizer, and Shire; has received writing assistance on projects from Adlon, Arbor, Ironshore, Neos, NextWave, Pfizer, Purdue, Rhodes Pharmaceuticals L.P., Shire and Tris; received payment for lectures from Arbor, Neos, Pfizer, Shire and Tris; has been an advisory board member for Arbor, Ironshore, Neos, Neurovance, NextWave, Noven, Pfizer, Purdue Pharma L.P. and Rhodes Pharmaceuticals L.P.; and has participated in speakers bureaus for Takeda. A.J.C. is a consultant to Adlon Therapeutics, Aevi Genomics, AiCure, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, MedAvante-ProPhase, Neos Therapeutics, NLS Pharma, Otsuka, Purdue, Shire, Sunovion, Supernus, Takeda, Tris Pharma; has received speaker/promotional honoraria from Adlon Therapeutics, Arbor Pharmaceuticals, Ironshore, Lundbeck, Neos Therapeutics, Otsuka, Shire, Sunovion, Takeda, Tris Pharma; has research grants from Aevi Genomics, Akili Interactive, Arbor Pharmaceuticals, Ironshore, KemPharm, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Shire, Sunovion, Supernus, Takeda, Tris Pharma; and is an employee and board member of the Neuroscience Education Institute. M.N.B. has served on advisory boards for Neos Therapeutics, Shire, and Tris Pharma, Inc., and has participated in speakers bureaus for Neos Therapeutics, Lundbeck, Otsuka, Sunovion Pharmaceuticals, Inc., Takeda, and Tris Pharma, Inc. G.A.E.D and S.B. are employees of Purdue Pharma (Canada). Medical writing services were provided by Susan Bartko-Winters, PhD, of SBW Medical Writing Inc., which was funded by Purdue Pharma (Canada).

Figures

FIG. 1.

Clinical trial design.

FIG. 2.

CONSORT diagram of subject disposition. AE, adverse event; DB, double-blind; OL, open-label.

FIG. 3.

Mean daily dose of PRC-063 by week for the dose-optimization period overlaid by mean (standard deviation) ADHD-RS-5 total score. ADHD-RS-5, attention-deficit/hyperactivity disorder-rating scale 5.

FIG. 4.

Mean SKAMP-C scores over the full classroom day. LS mean (standard error) SKAMP-C scores were measured predose and at eight postdose time points for subjects in the full analysis set (n = 147). SKAMP-C, Swanson, Kotkin, Agler, M-Flynn, and Pelham-Combined; LS, least squares.

FIG. 5.

PRC-063 improved PERMP-T scores at each time point during the 13-hour classroom day. LS, least squares; PERMP-T, Permanent Product Measure of Performance-Total.