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Clinical Trial
. 2018 Feb;28(1):10-18.
doi: 10.1089/cap.2017.0044. Epub 2017 Oct 17.

Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children With Attention-Deficit/Hyperactivity Disorder

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Free PMC article
Clinical Trial

Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children With Attention-Deficit/Hyperactivity Disorder

Ann Childress et al. J Child Adolesc Psychopharmacol. .
Free PMC article

Abstract

Objective: Current extended-release (ER) formulations of psychostimulants used for treatment of attention-deficit/hyperactivity disorder (ADHD) provide an extended duration of ADHD symptom control; however, the onset of efficacy can be protracted and variable, leaving the early morning untreated. The primary objective was to characterize the single-dose pharmacokinetics and tolerability of HLD200, an evening-dosed, delayed-release (DR) and ER formulation of methylphenidate (MPH), in healthy adults and in adolescents and children with ADHD.

Methods: The pharmacokinetics and tolerability of a single, oral evening dose of HLD200 (54 mg) were evaluated in two single-center open-label studies: the first in healthy adults (n = 12) and the second in adolescents (n = 18) and children (n = 11) with ADHD. Primary pharmacokinetic endpoints were the rate and extent of MPH absorption (Cmax and area under the curve [AUC]) and time to peak concentration (Tmax). These parameters were calculated using noncompartmental analysis.

Results: HLD200 produced a pharmacokinetic profile characterized by an 8- to 10-hour delay in MPH release, followed by a period of extended controlled release, resulting in an ascending absorption profile that coincided with the early morning and afternoon. Mean values (coefficient of variation [CV]%) of weight-adjusted pharmacokinetic parameters were similar in adults and in adolescents and children with ADHD: Cmax ([ng/mL]/[mg/kg]) was 9.1 (35.2), 8.8 (34.5), and 7.4 (30.1); AUC0-t ([ng · h/mL]/[mg/kg]) was 126.5 (35.5), 129.4 (34.8), and 129.7 (27.3); and Tmax (hours) was 15.6 (11.1), 17.1 (14.5), and 17.7 (14.1), respectively. Intersubject variability in the mean time to achieve ascending plasma MPH concentrations of 2, 3, 4, and 5 ng/mL was low (CV: 7.8%-17.7%).

Conclusions: Evening-dosed HLD200 produces the intended DR and ER pharmacokinetic profile that provides a consistent predictable delay in initial MPH release until the early morning, followed by extended release across the day. The body weight-adjusted pharmacokinetics of HLD200 were similar between adults and adolescents and children with ADHD.

Trial registration: ClinicalTrials.gov NCT01907360.

Keywords: attention-deficit/hyperactivity disorder; delayed-release; extended-release; methylphenidate; pharmacokinetics.

Figures

<b>FIG. 1.</b>
FIG. 1.
Dose–weight-normalized mean plasma MPH concentration–time profiles following an evening single-dose administration of HLD200 (54 mg) in healthy adults (≥18 years) and in children (6–12 years) and adolescents (13–17 years) with attention-deficit/hyperactivity disorder. Error bars represent ± SD of the mean. MPH, methylphenidate; SD, standard deviation.

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