An Open-Label, Multicenter, Single-Dose Pharmacokinetic Study of a Novel Amphetamine Extended-Release Orally Disintegrating Tablet in Preschool-Aged Children.

Abstract

Objective: In the U.S. ∼33% of children with attention-deficit/hyperactivity disorder (ADHD) are diagnosed during their preschool years (<6 years of age). The majority of these children are treated with a psychopharmacological treatment, despite limited data on pharmacokinetics (PKs), efficacy, or safety of these medications in this population. A phase 4, single-dose open-label study was conducted to assess the PK profile of amphetamine extended-release orally disintegrating tablets (AMP XR-ODT) under fasted conditions in preschool-aged children with ADHD. Methods: Preschool-aged children (aged 4 to <6 years) with a confirmed ADHD diagnosis were enrolled and administered AMP XR-ODT 3.1\u2009mg under fasted conditions. Plasma samples were analyzed for d- and l-amphetamine (AMP) via liquid chromatography-tandem mass spectrometry. Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf), area under the concentration-time curve from time 0 to the last measurable plasma concentration (AUC0-T), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), terminal half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) for d- and l-AMP and safety were assessed. Results: The PK and safety analyses included 15 preschool-aged children (4 years old, n\u2009=\u20096; 5 years old, n\u2009=\u20099); 14 completed the study. Quantifiable plasma concentrations for d- and l-AMP were observed 1.5 hours postdose and throughout the 24-hour sampling period. For d- and l-AMP, mean AUC0-inf was 315.2 and 104.4\u2009h·ng/mL, AUC0-T was 296.0 and 96.8\u2009h·ng/mL, t1/2 was 8.0 and 9.2 hours, Cmax was 23.0 and 7.0\u2009ng/mL, Tmax was 3.9 and 4.0 hours, CL/F was 6996.3 and 6837.1\u2009mL/h, and Vz/F was 75,874.5 and 84,140.0\u2009mL, respectively. Adverse events included tachycardia (n\u2009=\u20092), neutropenia (n\u2009=\u20091), increased alanine aminotransferase (n\u2009=\u20091), and aspartate aminotransferase (n\u2009=\u20091). Conclusions: AMP XR-ODT 3.1\u2009mg was well tolerated in preschool-aged children, with detectable plasma AMP concentrations over 24 hours, and a PK profile consistent with once-daily dosing.