A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults

Objectives: In this pharmacokinetic (PK) study in healthy adults, we sought to: (1) compare the PK properties of a novel amphetamine extended-release orally disintegrating tablet formulation (Adzenys XR-ODT? AMP XR-ODT]) to a reference extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the effect of food on AMP XR-ODT.

Methods: Forty-two adults were enrolled in a single-dose, open-label, 3-period, 3-treatment, randomized crossover study and received an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma concentration (C_max), time to maximum plasma concentration (T_max), elimination half-life (T_1/2), area under the concentration-time curve from time zero to last quantifiable concentration (AUC_last), from time zero to infinity (AUC_inf), relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed. The PK parameters were compared across treatments using an ANOVA. Safety was also assessed.

Results: A total of 39 adults completed this study. The geometric mean ratios (90% confidence interval CI]) for AMP XR-ODT/MAS ER C_max, AUC_5-last, AUC_last, and AUC_inf were within 80%–125% for both d-and l-amphetamine. The 90% CIs for AUC_0-5 were slightly below the 80%–125% range. When AMP XR-ODT was administered with food, there was a slight decrease in the d-and l-amphetamine C_max and approximately a 2-hour delay in T_max. The most common adverse events reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness, headache, anxiety, and nasal congestion.

Conclusions: AMP XR-ODT displayed a PK profile similar to MAS ER, and no clinically relevant food effect was observed.