Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting

Ann C Childress, Scott H Kollins, Andrew J Cutler, Andrea Marraffino, Carolyn R Sikes, Ann C Childress, Scott H Kollins, Andrew J Cutler, Andrea Marraffino, Carolyn R Sikes

Abstract

Objective: Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.

Methods: Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS).

Results: The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p < 0.0001). The effect was evident at 1 hour and lasted through 12 hours postdose. The average SKAMP-Attention, SKAMP-Deportment, PERMP-A, and PERMP-C scores were indicative of significantly greater ADHD symptom control for the MPH XR-ODT group. The most common AEs reported were decreased appetite, upper abdominal pain, headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting.

Conclusions: MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ).

Keywords: ADHD; MPH XR-ODT; classroom study; efficacy; safety.

Conflict of interest statement

Dr. A.C.C. has received research support from, consulted with, acted as an invited speaker for, and/or served on advisory boards for Alcobra Pharma, Arbor Pharmaceuticals, Forest Research Institute, Ironshore Pharmaceuticals, Lilly USA, Lundbeck, Neos Therapeutics, Neurovance, NextWave Pharmaceuticals, Noven Pharmaceuticals, Otsuka Pharmaceutical, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Shire Pharmaceuticals, Sunovion Pharmaceuticals, Theravance Biopharma, and Tris Pharma.

Dr. S.H.K. has received research support from and/or consulted with Akili Interactive; Alcobra Pharma; Arbor Pharmaceuticals; Atentiv; National Institutes of Health (NIDA, NIEHS, NICHD); Neos Therapeutics, Neurovance; Purdue Pharma; Rhodes Pharmaceuticals; Shire Pharmaceuticals; Sunovion Pharmaceuticals; Tris Pharma; and US Environmental Protection Agency.

Dr. A.J.C. has received research support from, consulted with, and/or acted as an invited speaker for Akili Interactive; Arbor Pharmaceuticals; AstraZeneca; Janssen Pharmaceuticals; Lilly; Lundbeck; Neos Therapeutics; Neurovance; Novartis Pharmaceuticals; Noven Pharmaceuticals; Otsuka Pharmaceutical; Pfizer; Purdue Pharma; Rhodes Pharmaceuticals; Shire Pharmaceuticals; Sunovion Pharmaceuticals; Supernus Pharmaceuticals; Takeda Pharmaceuticals; and Teva Pharmaceutical.

Dr. C.R.S. is an employee of Neos Therapeutics and has stock options. Dr. Sikes has stock in Pfizer.

Dr. A.M. has no financial relationships to disclose.

Figures

FIG. 1.
FIG. 1.
MPH XR-ODT Laboratory Classroom Study Design. Subjects were screened, underwent drug washout, and then entered an open-label dose-optimization period. Study drug was adjusted during those 4 weeks to the best dose, based on tolerability and efficacy, and then entered a 1-week dose stabilization period. At visit 8, the optimal dose of MPH XR-ODT or placebo was dispensed. MPH XR-ODT or placebo was administered by study staff at visit 8. Subjects returned for safety assessments at visit 9 and a follow-up call was completed ∼1 month later. MPH XR-ODT, methylphenidate extended-release orally disintegrating tablet.
FIG. 2.
FIG. 2.
The Separation of Between-Group SKAMP-Combined Scores over the Classroom Day. SKAMP-Combined scores were measured predose and at seven postdose time points for participants in the full analysis set (n = 82). Data from all time points postdosing were compared for descriptive purposes using repeated measures ANCOVA on the postdose scores. ANCOVA, analysis of covariance; LS, least squares; MPH XR-ODT methylphenidate extended-release orally disintegrating tablet; NS, non-signficant; SE, standard error of the mean; SKAMP, Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale.
FIG. 3.
FIG. 3.
MPH XR-ODT Improved PERMP-A and PERMP-C Scores. PERMP-A and PERMP-C scores were measured predose and at seven postdose time points for participants in the full analysis set (n = 82) on MPH XR-ODT or placebo (p values: gray = PERMP-A, black = PERMP-C). LS, least squares; MPH XR-ODT, methylphenidate extended-release orally disintegrating tablet; NS, non-significant; PERMP-A, permanent product measure of performance-attempted; PERMP-C, permanent product measure of performance-correct; SE, standard error of the mean.

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