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

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 mg 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 (AUC _0-inf ), area under the concentration-time curve from time 0 to the last measurable plasma concentration (AUC _0-T ), maximum plasma concentration (C _max ), time to maximum plasma concentration (T _max ), terminal half-life (t _1/2 ), 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  = 6; 5 years old, n  = 9); 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 AUC _0-inf was 315.2 and 104.4 h·ng/mL, AUC _0-T was 296.0 and 96.8 h·ng/mL, t _1/2 was 8.0 and 9.2 hours, C _max was 23.0 and 7.0 ng/mL, T _max was 3.9 and 4.0 hours, CL/F was 6996.3 and 6837.1 mL/h, and Vz/F was 75,874.5 and 84,140.0 mL, respectively. Adverse events included tachycardia ( n  = 2), neutropenia ( n  = 1), increased alanine aminotransferase ( n  = 1), and aspartate aminotransferase ( n  = 1). Conclusions: AMP XR-ODT 3.1 mg was well tolerated in preschool-aged children, with detectable plasma AMP concentrations over 24 hours, and a PK profile consistent with once-daily dosing.