PMID- 33090921 OWN - NLM STAT- MEDLINE DCOM- 20210923 LR - 20210923 IS - 1557-8992 (Electronic) IS - 1044-5463 (Print) IS - 1044-5463 (Linking) VI - 30 IP - 10 DP - 2020 Dec TI - 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. PG - 580-589 LID - 10.1089/cap.2020.0109 [doi] AB - 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. FAU - Childress, Ann C AU - Childress AC AD - Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, Nevada, USA. FAU - Brams, Matthew N AU - Brams MN AD - Bayou City Research, Ltd., Houston, Texas, USA. FAU - Cutler, Andrew J AU - Cutler AJ AD - Neuroscience Education Institute, Lakewood Ranch, Florida, USA. AD - Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA. FAU - Donnelly, Graeme A E AU - Donnelly GAE AD - Purdue Pharma (Canada), Pickering, Canada. FAU - Bhaskar, Sailaja AU - Bhaskar S AD - Imbrium Therapeutics L.P., a subsidiary of Purdue Pharma L.P., Stamford, Connecticut, USA. LA - eng SI - ClinicalTrials.gov/NCT03172481 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201022 PL - United States TA - J Child Adolesc Psychopharmacol JT - Journal of child and adolescent psychopharmacology JID - 9105358 RN - 0 (Central Nervous System Stimulants) RN - 0 (Delayed-Action Preparations) RN - 207ZZ9QZ49 (Methylphenidate) SB - IM MH - Attention Deficit Disorder with Hyperactivity/*drug therapy MH - Central Nervous System Stimulants/adverse effects/*therapeutic use MH - Child MH - Delayed-Action Preparations/adverse effects/*therapeutic use MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Methylphenidate/adverse effects/*therapeutic use MH - Treatment Outcome PMC - PMC7757528 OTO - NOTNLM OT - Adhansia OT - Foquest OT - PRC-063 OT - attention-deficit/hyperactivity disorder OT - laboratory classroom study OT - methylphenidate COIS- 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). EDAT- 2020/10/23 06:00 MHDA- 2021/09/24 06:00 PMCR- 2020/12/03 CRDT- 2020/10/22 17:31 PHST- 2020/10/23 06:00 [pubmed] PHST- 2021/09/24 06:00 [medline] PHST- 2020/10/22 17:31 [entrez] PHST- 2020/12/03 00:00 [pmc-release] AID - 10.1089/cap.2020.0109 [pii] AID - 10.1089/cap.2020.0109 [doi] PST - ppublish SO - J Child Adolesc Psychopharmacol. 2020 Dec;30(10):580-589. doi: 10.1089/cap.2020.0109. Epub 2020 Oct 22.